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Research & Scholarship

Current Research and Scholarly Interests

Improving Access to Family Planning Services in Low Resource Settings:

Through a collaboration with Population Services International, the Stanford Program for International Reproductive Education and Services (SPIRES) provides technical direction in a program designed to improve access to and uptake of family planning, particularly Long Acting Reversible Contraception (LARC) such as IUDs and implants, in 14 developing countries globally. The first year saw insertion of over 280,000 IUDs.

Clinical Trials

A common practice for preparation for surgical abortion after 19 weeks gestation is the
placement of multiple sets of osmostic dilators 1-2 days prior to the procedure. The
investigators aim to study the addition of mifepristone as an adjunct to cervical dilation
prior to abortion between 19-24 weeks gestation, and its potential to minimize the number of
painful procedures and time in clinic (or away from work/home) that multiple sets of dilators
can require. The investigators hypothesize that one set of dilators with mifepristone will
result in similar procedure times and decreased "total" time as two sets of dilators.

Exploring Semi-Quantitative Pregnancy Tests and Their Impact on Reproductive Health Service ProvisionNot Recruiting

This study will examine the feasibility, practicality, utility and usability of a
semi-quantitative urine pregnancy test (dBest One Step hCG Panel Test Kit) recently approved
by the food and drug administration (FDA) for both Professional (physician office) and
over-the-counter (consumer) use. The study seeks to:
1. Assess the correlation of this pregnancy test results with serum values (as distinct
from urine) hCG.
2. Assess whether or not time of day of urine collection has any impact on the outcome of
the dBest test.
3. Assess user comprehension of the pregnancy test, especially assessment of the result.

Stanford is currently not accepting patients for this trial.For more information, please contact Kelsey Lynd, (650) 721 - 1237.

Given the potential of semi-quantitative pregnancy tests as part of assisted fertility care,
the investigators would like to document the feasibility and acceptability of a
semi-quantitative pregnancy test as an adjunct to or replacement of current monitoring
protocols to offer women and health care providers a new choice of diagnostic tools to
confirm early pregnancy. The pilot will help us to better understand how this tool
complements existing monitoring protocols. If a suitable addition or replacement to repeat
blood draws for serum hCG assessment, the SQPT could also contribute to efforts to make
assisted fertility treatments more patient-friendly. This study seeks to test this innovation
by asking women assigned to perform a Quanti5 Multilevel hCG Pregnancy Test (Athenium
Pharmaceuticals, LLC, Nashville, TN) at home on a weekly basis for up to 4 weeks after egg
retrieval/embryo transfer or intrauterine insemination.
The investigators hypothesize that the test, which can be used at home by women, will provide
confirmation of the presence of a pregnancy compared with standard serum hCG testing because
1) it has sensitivity and specificity that correlates well with serum testing, and 2) it can
be used at home and thus earlier to determine presence of hCG.

The purpose is to investigate how menstrual blood differs from systemic blood to evaluate if
menstrual blood could be utilized as a natural and non-invasive access to blood for regular
health monitoring and early diagnostics.

This is a randomized controlled trial that compares traditional IUD insertion with that of a
no uterine sound, no bimanual pelvic exam approach. The investigators hypothesis is that IUD
placement is safe and effective without pre-procedural assessment of uterine size, direction,
or depth.

Stanford is currently not accepting patients for this trial.For more information, please contact Klaira M Lerma, MPH, 650-721-1562.

Exploring the Role of At-home Semi-Quantitative Pregnancy Tests for Medical Abortion Follow-upRecruiting

This study will examine the feasibility, acceptability and usability of a semi-quantitative
urine pregnancy test (dBest One Step hCG Panel Test Kit) for at-home follow-up after early
medical abortion using mifepristone+misoprostol. The study seeks to:
1. Assess the feasibility of using this test in lieu of standard one-week clinic-based
follow up for determination of complete abortion status as part of normal service
delivery. In Mexico, follow up will be in two weeks, as is standard care in that .
2. To determine if women using this test at home understand how to use it and can correctly
interpret the results; is it practical.
3. Assess women's and provider's acceptability of using at-home pregnancy tests in lieu of
clinic-based follow up for confirmation of complete medical abortion in the future.

Abstract

To compare pain control at various time points during first-trimester surgical abortion using a patient-administered lidocaine gel compared with a traditional lidocaine paracervical block.We conducted a randomized controlled trial of women undergoing surgical abortion at less than 12 weeks of gestation in an outpatient setting. The primary outcome was pain at cervical dilation as measured on a 100-mm visual analog scale. A sample size of 142 participants was planned to detect a 15-mm or greater difference on the 100-mm visual analog scale with 90% power and a significance level of .025, adding 10% for participant dropout and protocol violations. Participants received either 12 mL of a 1% lidocaine paracervical block or 20 mL of a self-administered, 2% lidocaine gel 20-30 minutes before procedure initiation. Secondary outcomes included anticipated pain, baseline pain, pain with speculum and tenaculum placement, pain after suction aspiration, and pain 30-45 minutes postoperatively.From April to October 2015, a total of 142 women were enrolled (68 in the paracervical block group, 69 in the gel group, and five not analyzed as a result of participant withdrawal). Sociodemographic characteristics were similar between groups. The mean pain score with cervical dilation was 60 mm (95% confidence interval [CI] 54-66) in the paracervical block group and 64 mm (95% CI 59-69) in the gel group (P=.3). There was no significant difference between mean pain scores at any time points measured.Self-administration of lidocaine gel before first-trimester surgical abortion is noninferior to a traditional paracervical lidocaine block and should be considered as an alternative, noninvasive approach to pain control for first-trimester surgical abortion.ClinicalTrials.gov, https://clinicaltrials.gov, NCT02447029.

Abstract

To evaluate the accuracy, feasibility and acceptability of two urine pregnancy tests in assessing abortion outcomes at three time points after mifepristone administration.This randomized trial enrolled women seeking early medical abortion at two hospitals in Vietnam. Investigators randomly allocated participants to at-home administration of a multilevel urine pregnancy test (MLPT) or a high sensitivity urine pregnancy test (HSPT) to assess their abortion outcomes. A baseline test was administered on the same day as mifepristone. Participants performed and interpreted results of pregnancy tests taken 3, 7 and 14days after mifepristone. Ultrasound exam determined continuing pregnancy.Six hundred women enrolled, and 300 received each test. A percentage of 97.4 (584) had follow-up, of whom 13 women had continuing pregnancies. The specificity of MLPT at detecting absence of continuing pregnancy was 63.9%, 90.4% and 97.1% at study day 3, 7 and 14. The specificity of HSPT was 6.0%, 19.8% and 62.2%, respectively. The positive predictive value (PPV) of MLPT at detecting continuing pregnancy was 6.4% at day 3 and rose to 46.7% at day 14. In contrast, the PPV for HSPT was 2.2% at day 3 and rose to 6.5% at day 14. At all three time points, the sensitivity and negative predictive values for both tests were 100.0%. Most women found their assigned tests easy to use and would prefer future home follow-up with a pregnancy test.The MLPT enables women to assess their abortion outcomes more reliably than with HSPT. With MLPT, women can know their outcomes as early as 3 days after mifepristone.Medical abortion service delivery with an MLPT to obtain a baseline (preabortion) human chorionic gonadotropin (hCG) estimate and a second follow-up MLPT 1 to 2 weeks later can establish whether there has been a drop in hCG, signifying absence of a continuing pregnancy. Used this way, MLPTs can enable women to assess their abortion status outside of a clinic setting and without serum hCG testing and/or ultrasound.

Abstract

To explore a simplified technique for intrauterine device (IUD) insertion.The present prospective longitudinal study enrolled patients aged at least 18years presenting at the gynecology clinic of Stanford University for IUD insertion between June 1, 2013 and June 30, 2014. No pelvic examination or uterine sounding was performed prior to IUD insertion. Transvaginal ultrasonography was performed immediately after insertion and at 4-6weeks to confirm device placement. The primary outcome was successful IUD placement.The study enrolled 50 patients. IUD insertion was completed successfully without any cervical manipulation in 40 (80%) participants. Sounding was not needed for any procedures. A cervical dilator was required to locate the internal os for 10 (20%) patients. The mean distance between IUDs and the endometrial verge immediately following insertion was 2.9mm. IUD insertion was rated "difficult" by the physician performing the procedure in 3 (6%) patients. No perforations were recorded. IUD expulsion occurred in 3 (6%) patients; menorrhagia was the indication for IUD insertion in two of these patients.IUD insertion without prior pelvic examination and sounding was feasible; this technique could reduce the need for instrument use during insertion and, consequently, the pain associated with insertion.

Abstract

The objective was to investigate mifepristone as a potential adjunct to cervical preparation for surgical abortion after 19weeks of gestation, with the aim of improving procedure access, convenience and comfort.This is a site-stratified, block-randomized, noninferiority trial of 50 women undergoing surgical abortion between 19 and 23 6/7weeks of gestation randomized to receive either one set of osmotic dilators plus mifepristone the day prior to procedure (mifepristone group) or two sets of osmotic dilators (placed 18-24 h apart) in the 2 days prior to procedure (control group). All subjects received preprocedure misoprostol. Primary outcome was procedure time. Secondary outcomes included preoperative cervical dilation, ease of procedure, and side effects and pain experienced by subjects.Mean gestational age was similar between groups (20weeks); more nulliparous subjects were randomized to the mifepristone group (46% vs. 12%, p=.009). Mean procedure times were similar: mifepristone group 11:52 (SD 5:29) vs. control group 10:56 (SD 5:08); difference in means -56s, with confidence interval (95% CI -4:09 to +2:16) not exceeding the 5-min difference we a priori defined as clinically significant. Preprocedure cervical dilation did not differ and was >3cm for the majority of subjects in both groups. There was no difference (p=.6) in ease of procedure reported by providers. Preoperative (postmisoprostol) pain and postoperative pain levels were greater with mifepristone (p = 0.02 and p= 0.04 respectively). Overall subject experience was not different (p=0.80), with most reporting a "better than expected" experience.Mifepristone with one set of osmotic dilators and misoprostol did not result in longer procedure times or less cervical dilation than serial (two sets) of osmotic dilators and misoprostol, and has the potential to improve access to second trimester abortion without compromising safety.Use of mifepristone for cervical preparation before surgical abortion after 19weeks allows for fewer visits and fewer osmotic dilators without compromising cervical dilation or increasing procedure time.

Abstract

OBJECTIVE: This study aimed to assess the safety, acceptability and feasibility of primary human papillomavirus (HPV) testing for cervical cancer prevention at the community level in a low-resource setting. MATERIALS AND METHODS: After training a technician to run specimens on the careHPV unit, the study team traveled to a different village each day in rural Roi-et Province, Thailand. Women were tested for HPV using self-swab, followed by careHPV testing. Those with positive result were assessed immediately by visual inspection with acetic acid. Women positive for HPV and visual inspection with acetic acid were offered cryotherapy. Safety was determined by monitoring adverse events. Exit surveys assessed acceptability and feasibility. Feasibility was also assessed by measuring testing and triage throughputs. RESULTS: Technician training required 2.5 days to achieve competency. A total of 431 women were screened in 14 days, with an average of 31 women screened daily. No adverse events were reported. Women deemed the program overwhelmingly acceptable: 90.5% reported that they would take the self-swab again, 71.3% preferred the self-swab to a clinician swab. The program was also feasible: 99.8% of eligible women agreed to testing, 94.8% returned for same-day follow-up, and women only spent 30 to 50 minutes of their total time with the program from screening to results. CONCLUSIONS: Cervical cancer prevention programs based on self-swab HPV testing could be safe, acceptable, feasible, and effective at the community level in low-resource settings.

Abstract

To examine the effect of the interval between mifepristone and misoprostol administration on induction time (first misoprostol dose to abortion), total procedure time (mifepristone administration to abortion), and safety and efficacy in second-trimester induction abortion (13-24 weeks).We searched MEDLINE (1966-2012), ClinicalTrials.gov, POPLINE, and the Cochrane Controlled Trials Register using search terms for second trimester, abortion, misoprostol, and mifepristone and reviewed reference lists of published reports.Our search revealed 138 articles of which 29 met inclusion criteria: 20 randomized controlled trials and nine observational studies. Studies were included if, in any study arm, mifepristone and misoprostol were used for medical abortion in the second trimester.Two authors independently reviewed the articles and abstracted the data using standardized data abstraction templates to summarize data. Discrepancies were resolved by consensus. Three studies directly compared a 1-day to 2-day mifepristone-misoprostol interval; they showed small differences in median induction times (weighted average 7.3 hours, range 7-8.5 for a 1-day interval; weighted average 6.8 hours, range 6.3-7.2 for a 2-day interval) and no significant difference in percent expelled by 12 hours or 24 hours. When all randomized studies using mifepristone and misoprostol were pooled by comparable mifepristone-misoprostol interval and misoprostol dose, induction times (first misoprostol dose to expulsion) were only 1-2 hours longer for a 12- to 24-hour interval compared with a 36-48-hour interval, whereas total abortion times (mifepristone to expulsion) were at least 18 hours longer in the 36- to 48-hour group. Induction times varied by misoprostol dosing, with 400-microgram misoprostol protocols resulting in shorter induction times than 200-microgram protocols.Shortening the mifepristone-misoprostol interval, thereby reducing total abortion time, does not compromise the safety or efficacy of second-trimester medication abortion and may be used to accommodate patient or health care provider preference.

Abstract

To simplify follow-up after medical abortion by examining whether women could use a semi-quantitative pregnancy test at home to screen for ongoing pregnancy.Three hundred women seeking medical abortion at a tertiary hospital in Vietnam participated in the study. Participants used a semi-quantitative pregnancy test at the hospital to estimate baseline human chorionic gonadotropin (hCG) levels and administered another test at home 2 weeks later for comparison. Women interpreted the test result at home and then returned to hospital for follow-up care. At this visit, self-assessment was verified. To assess further the feasibility of the test as a follow-up tool in service delivery, 200 additional women completed a user comprehension survey.The tests identified all 11 ongoing pregnancies among study participants (100% sensitivity; 89.7% specificity). Women reported that the test was easy to use (255/292 [87.3%]) and that provider instructions helped them to use the test (291/292 [99.7%]).Semi-quantitative pregnancy tests offer high sensitivity and negative predictive value. If user instructions can be further simplified, the tests could be used in lieu of transvaginal ultrasound and/or serum hCG at clinic-based follow-up or by women themselves for home-based follow-up. Clinical trials.gov:NCT01150279.

Abstract

Contraception in many developing countries is characterized by high unmet need, irregular access, low utilization and presumed demand for long-acting reversible contraceptives (LARCs).A 13-country initiative focused on increasing consumer demand and high quality services for intrauterine devices (IUDs) began in 2009. Services were provided through (a) private sector-franchised or affiliated clinics; (b) providers seconded to the public sector and (c) special "event" days. Client intake data are used to compare the profile of IUD acceptors with IUD users from representative national datasets of select countries, as well as examine trends in IUD uptake.During 2009-2010, 575,601 IUDs were inserted across the 13 countries. Compared to national IUD users, users in this project were slightly younger and less educated. Among IUD acceptors, 24% used no modern method at the time of IUD initiation, and 28% reported injectable use in the three previous months.Convenient, quality, affordable services with demand creation can result in significant uptake of LARCs in settings with low use.

Abstract

Medical abortion in the United States requires clinic-based follow-up, representing additional time and cost to women and clinics. We studied a semi-quantitative home pregnancy test as a possible replacement for in-person follow-up.Four hundred and ninety women participated in the clinical study and used a pregnancy test to determine baseline human chorionic gonadotropin (hCG) on the day of mifepristone administration and follow-up hCG 1 week later. One hundred and eighty-nine other women completed a user comprehension survey. Accuracy, feasibility and acceptability of the test were assessed in both the clinical study and the survey.The test identified the one ongoing pregnancy in the clinical study cohort. Sensitivity and specificity were calculated at 100.0% and 97.0%. The majority of participants in both the clinical study and the user comprehension survey found the test to be "very easy" or "easy" to use.At-home follow-up with a semi-quantitative pregnancy test is feasible for service delivery in the United States.

Abstract

To explore the feasibility of competency-based training of Zambian nurse-midwives in postplacental and postpartum intrauterine device (PPIUD) insertion and to estimate learning curves for this procedure.A pilot service-delivery project was conducted, involving 9 nurse-midwives who participated in a 10-day PPIUD insertion training course at the University Teaching Hospital, Lusaka, Zambia. US and Zambian clinicians taught the didactic and practical curriculum. Checklists were used for standardization and a pelvic model was developed to achieve PPIUD insertion competency in the classroom before moving to clinical practice. Patients were recruited during prenatal visits, in early labor, and postpartum. Informed, voluntary consent was obtained. All clinical PPIUD insertions were supervised or performed by experienced trainers.All 9 nurse-midwives achieved competency on the pelvic model after 3 attempts. During the training period, 38 PPIUDs were inserted in postpartum women; no complications occurred. By the end of training, 4 of the nurse-midwives were deemed competent to independently insert PPIUDs. On average, 4 PPIUD insertions were needed to achieve clinical competency.Concentrated, competency-based training in PPIUD insertion is feasible in an African setting. Replication of such training could increase the popularity and prevalence of PPIUD use among African women.

Abstract

As a result of widespread screening and treatment programs, the incidence of cervical cancer has decreased by as much as 75% in the developed world. Commonly used treatment modalities for precancerous lesions include cone biopsy, the Loop Electrosurgical Excision Procedure (LEEP), laser ablation and cryotherapy. In recent years LEEP has replaced cryotherapy as a commonly provided outpatient procedure in many places; however increased awareness of the burden of cervical cancer in the developing world and increased awareness of long term consequences of LEEP ‑ such as cervical insufficiency ‑ have renewed interest in cryotherapy. We reviewed current literature addressing the technique, efficacy, safety and acceptability of cryotherapy, as well as special topics such as cost effectiveness, HIV, and low resource settings. Among studies we reviewed, cure rates ranged from 56.8-96.6% among prospective controlled trials and from 70-95.5% among observational studies. Cryotherapy has very low complication rates and serious complications requiring medical intervention or affecting future reproductive outcomes are extremely rare. Side effects including vaginal discharge and cramping are temporary, generally self-limited, and well tolerated after anticipatory patient counseling. When surveyed, women find cryotherapy highly acceptable. Compared to other treatment modalities, cryotherapy is very affordable and feasible to integrate into cervical cancer screening and treatment programs.

Abstract

Injectable contraceptives are now the most popular contraceptive methods in sub-Saharan Africa. Injectables have not been an option for African women lacking convenient access to health facilities, however, since very few family planning programmes permit community-based distribution (CBD) of injectables by non-medically trained workers. Committed to reducing unmet contraceptive need among remote, rural populations, the Ministry of Health and Family Planning (MOHFP) of Madagascar sought evidence regarding the safety, effectiveness and acceptability of CBD of injectables.The MOHFP joined implementing partners in training 61 experienced CBD agents from 13 communities in provision of injectables. Management mechanisms for injectables were added to the CBD programme's pre-existing systems for record keeping, commodity management and supervision. After 7 months of service provision, an evaluation team reviewed service records and interviewed CBD workers and their supervisors and clients.CBD workers demonstrated competence in injection technique, counselling and management of clients' re-injection schedule. CBD of injectables appeared to increase contraceptive use, with 1662 women accepting injectables from a CBD worker. Of these, 41% were new family planning users. All CBD agents wished to continue providing this service, and most supervisors indicated the programme should continue. Nearly all clients interviewed said they intended to return to the CBD worker for re-injection and would recommend this service to a friend.This experience from Madagascar is among the first evidence from sub-Saharan Africa documenting the feasibility, effectiveness and acceptability of CBD services for injectable contraceptives. This evidence influenced national and global policy makers to recommend expansion of the practice. CBD of injectables is an example of effective task shifting of a clinical practice as a means of extending services to underserved populations without further burdening clinicians.

Abstract

Despite increasing contraceptive availability, unintended pregnancy remains a global problem, representing as many as 30% of all known pregnancies. Various strategies have been proposed to reverse this disturbing trend, especially increased use of long-acting reversible contraceptive (LARC) methods. In this review we aim to discuss the role of LARC methods and importance of contraceptive counseling in reducing unintended pregnancy rates.References/resources cited were identified based on searches of medical literature (MEDLINE, 1990-2009), bibliographies of relevant publications and the Internet.LARC methods-copper intrauterine devices (IUDs), progestogen-releasing intrauterine system and injectable and implantable contraceptives-are safe and effective contraceptive options (unintended pregnancy rates with typical versus perfect use: 0.05-3.0 versus 0.05-0.6%) that are appropriate for a wide range of women seeking to limit or space childbearing. Despite their safety and efficacy records, these methods remain underutilized; injectable and implantable methods are used by an estimated 3.4% and intrauterine methods by 15.5% of women worldwide. LARC methods require no daily or coital adherence and avoid the adverse events and health risks of estrogen-containing contraceptives. The copper IUD and progestin-only injections and implants have been shown to be more cost-effective than more commonly used methods, such as condoms and the pill (5-year savings: $13,373-$14,122, LARC; $12,239, condoms; $12,879, pill). Women who are considering use of LARC methods should receive comprehensive contraceptive counseling, as women who receive counseling before use demonstrate higher rates of after-use method satisfaction, continuation and acceptance than those who do not.

Abstract

The purpose of this study was to assess the safety and acceptability of a single-visit approach to cervical cancer prevention combining visual inspection of the cervix with acetic acid wash (VIA) and cryotherapy.The study was observational. Nine clinicians were trained in VIA and cryotherapy. Over 18 months 3665 women were VIA-tested. If positive and eligible, cryotherapy was offered immediately. Treated women were followed-up at 3 months and 1 year.The test-positive rate was 13.2%. Of those eligible, 70.2% and 21% received immediate or delayed treatment, respectively. No major complications were recorded, and 5.6% presented for a perceived problem post-cryotherapy. Among those treated over 90% expressed satisfaction with their experience, and 96% had an indentifiable squamo-columnar junction. Only 2.6% (6/232) were test positive, 1-year posttreatment.A single-visit approach using VIA and cryotherapy proved to be safe, acceptable, and feasible in an urban African setting.

Abstract

The dilation and evacuation (D&E) procedure was modified for use in a low-resource setting where access to electric vacuum aspiration is limited.In this demonstration project, buccal misoprostol is used for cervical preparation, followed by evacuation using manual vacuum aspiration (MVA) and forceps. Senior physicians at the Hanoi Obstetrics and Gynecology Hospital were trained in D&E and subsequently conducted 439 D&E procedures.The primary outcomes were efficacy and safety. Secondary outcome measures include efficacy of buccal misoprostol for cervical preparation prior to D&E and the feasibility of MVA for use in the D&E procedure.Successful abortion took place in 100% of the cases. Three major complications occurred. This procedure may be appropriate in other low-resource settings lacking safe, effective abortion services in the second trimester.

Abstract

To increase screening and treatment coverage, innovative approaches to cervical-cancer prevention are being investigated in rural Thailand. We assessed the value of a single-visit approach combining visual inspection of the cervix with acetic acid wash (VIA) and cryotherapy.12 trained nurses provided services in mobile (village health centre-based) and static (hospital-based) teams in four districts of Roi-et Province, Thailand. Over 7 months, 5999 women were tested by VIA. If they tested positive, after counselling about the benefits, potential risks, and probable side-effects they were offered cryotherapy. Data measuring safety, acceptability, feasibility, and effort to implement the programme were gathered.The VIA test-positive rate was 13.3% (798/5999), and 98.5% (609/618) of those eligible accepted immediate treatment. Overall, 756 women received cryotherapy, 629 (83.2%) of whom returned for their first follow-up visit. No major complications were recorded, and 33 (4.4%) of those treated returned for a perceived problem. Only 17 (2.2%) of the treated women needed clinical management other than reassurance about side-effects. Both VIA and cryotherapy were highly acceptable to the patients (over 95% expressed satisfaction with their experience). At their 1-year visit, the squamocolumnar junction was visible to the nurses, and the VIA test-negative rate was 94.3%.A single-visit approach with VIA and cryotherapy seems to be safe, acceptable, and feasible in rural Thailand, and is a potentially efficient method of cervical-cancer prevention in such settings.

Abstract

The "boom and bust phenomenon" is a pattern that has emerged in the development, introduction, and delivery of a number of significant new contraceptive products in the United States. When a new contraceptive product is introduced with great promise and publicity, it usually experiences a "boom" during which sales, demand, and expectations are high. This boom is often followed by a "bust" phase during which a product does not live up to expectations, initial excitement falls off, and a drop in sales and use ensues. The boom and bust phenomenon goes to the heart of what some have referred to as the failed promise of the contraception revolution by creating obstacles to significant expansion of contraceptive choice in the United States. Case studies of oral contraceptives, intrauterine devices, and Norplant(R) are used to illustrate the boom and bust phenomenon and the effect it has had in shaping the direction of advances in contraceptive technology.

Abstract

Human pluripotent stem cells would be invaluable for in vitro studies of aspects of human embryogenesis. With the goal of establishing pluripotent stem cell lines, gonadal ridges and mesenteries containing primordial germ cells (PGCs, 5-9 weeks postfertilization) were cultured on mouse STO fibroblast feeder layers in the presence of human recombinant leukemia inhibitory factor, human recombinant basic fibroblast growth factor, and forskolin. Initially, single PGCs in culture were visualized by alkaline phosphatase activity staining. Over a period of 7-21 days, PGCs gave rise to large multicellular colonies resembling those of mouse pluripotent stem cells termed embryonic stem and embryonic germ (EG) cells. Throughout the culture period most cells within the colonies continued to be alkaline phosphatase-positive and tested positive against a panel of five immunological markers (SSEA-1, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) that have been used routinely to characterize embryonic stem and EG cells. The cultured cells have been continuously passaged and found to be karyotypically normal and stable. Both XX and XY cell cultures have been obtained. Immunohistochemical analysis of embryoid bodies collected from these cultures revealed a wide variety of differentiated cell types, including derivatives of all three embryonic germ layers. Based on their origin and demonstrated properties, these human PGC-derived cultures meet the criteria for pluripotent stem cells and most closely resemble EG cells.

Abortion choices among women in Cambodia after introduction of a socially marketed medicated abortion product.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and ObstetricsSotheary, K., Long, D., Mundy, G., Madan, Y., Blumenthal, P. D.2017; 136 (2): 205-209

Abstract

To assess whether a social marketing initiative focusing on medicated abortion via a mifepristone/misoprostol "combipack" has contributed to reducing unsafe abortion in Cambodia.In a questionnaire-based cross-sectional study, annual household surveys were conducted across 13 Cambodian provinces in 2010, 2011, and 2012. One married woman of reproductive age who was not pregnant and did not wish to be within the next 2 years in each randomly selected household was approached for inclusion. Participants were interviewed using a structured questionnaire.The questionnaire was completed by 1843 women in 2010, 2068 in 2011, and 2059 in 2012. Manual vacuum aspiration was reported by 61 (72.6%) of 84 women surveyed in 2010 who reported an abortion in the previous 12 months, compared with only 28 (52.8%) of 53 in 2012 (P=0.001). The numbers of women undergoing medicated abortion increased from 22 (26.2%) of 84 in 2010 to 27 (49.1%) of 53 in 2012 (P=0.003), whereas the numbers undergoing unsafe abortion decreased from 4 (4.8%) in 2010 to 0 in 2012 (P=0.051).Social marketing of medication abortion coupled with provider training in clinical and behavioral change could have contributed to a reduction in the prevalence of unsafe abortion and shifted the types of abortion performed in Cambodia, while not increasing the overall number of abortions.

Abstract

To summarize data on the accuracy of a strategy designed to exclude ongoing pregnancy after medical abortion treatment by observing a decline in urine human chorionic gonadotropin (hCG) concentration as estimated by multilevel urine pregnancy tests (MLPTs) performed before and after treatment.We collated original data from seven studies performed by our organization that evaluated the accuracy of the MLPT strategy for assessment of outcome of medical abortion. Our first analysis included data from the five studies in which each participant was evaluated both with the MLPT strategy and with ultrasound or other clinical assessment. Our second analysis combined data from two randomized trials that compared the MLPT strategy to assessment by ultrasound. Both analyses included only participants treated at ≤63 days of gestation.In the first analysis, 1482 (93%) of 1599 participants had a decline in hCG concentration after treatment. Twenty-one (1.3%) had an ongoing pregnancy, none of whom had a decline (predictive value 100%, 95% CI 93.3%, 100%). The remaining 96 women (6.0%) had no decline without an ongoing pregnancy. The second analysis, which included 3762 participants with follow-up, found no significant difference in the rates of ongoing pregnancy ascertained in the randomized groups (RR 0.88; 95% CI 0.50, 1.54). Nearly all of the post-treatment MLPTs in the seven studies (3484/3535; 99%) were performed by the participants themselves.Serial multilevel urine pregnancy testing is a highly reliable and efficient strategy for excluding ongoing pregnancy after medical abortion at≤63 days of gestation.Serial urine testing using MLPTs can obviate the need for routine ultrasound or examination after medical abortion treatment and can allow most women to avoid an in-person follow-up visit to the abortion facility.

Abstract

Emergency contraception provides a critical and time-sensitive opportunity for women to prevent undesired pregnancy after intercourse. Both access and available options for emergency contraception have changed over the last several years.Emergency contraceptive pills can be less effective in obese women. The maximum achieved serum concentration of levonorgestrel (LNG) is lower in obese women than women of normal BMI, and doubling the dose of LNG (3 mg) increases its concentration maximum, approximating the level in normal BMI women receiving one dose of LNG. Repeated use of both LNG and ulipristal acetate (UPA) is well tolerated. Hormonal contraception can be immediately started following LNG use, but should be delayed for 5 days after UPA use to avoid dampening the efficacy of UPA. The copper intrauterine device (IUD) is the only IUD approved for emergency contraception (and the most effective method of emergency contraception), but use of LNG IUD as emergency contraception is currently being investigated. Accurate knowledge about emergency contraception remains low both for patients and healthcare providers.Emergency contraception is an important yet underutilized tool available to women to prevent pregnancy. Current options including copper IUD and emergency contraceptive pills are safe and well tolerated. Significant gaps in knowledge of emergency contraception on both the provider and user level exist, as do barriers to expedient access of emergency contraception.

Abstract

The aim of the study was to assess continuation rates and satisfaction among post-partum intrauterine device (PPIUD) accepters.This prospective observational study comprised 591 Zambian women who underwent PPIUD insertion at sites of the Society for Family Health, Lusaka, Zambia. The women were contacted 6-12 months after PPIUD insertion and asked to return to the clinic for interview and examination. If the IUD strings were not visible, an ultrasound was performed. Participants were asked about their satisfaction with the PPIUD. Main outcome measures were short-term PPIUD continuation and reported complications according to time of insertion.Of 591 women enrolled, 305 women attended the follow-up appointment for interview and examination, giving a power of 80% to estimate an expulsion rate of 10 ± 5%. The IUD was inserted within 10 min of placental delivery (post-placental insertion) in 24.3% of participants (n = 74) and within 48 h (immediate post-partum insertion) in 71.1% of participants (n = 217). The total expulsion rate was 5.6%. Expulsion rates for post-placental and immediate post-partum insertions were 10.8% and 4.1%, respectively. No significant difference in expulsion rates was found (p = 0.10). Of those with an expulsion, 76.5% (n = 13) recognised that it had occurred. There were no reported complications, and 94.1% of women reported being satisfied or very satisfied with their PPIUD (n = 287).Overall, expulsion rates were lower than previously reported, particularly for immediate post-partum insertions. Attention to high fundal placement at insertion is a likely explanation for the low expulsion rates. Contrary to conventional wisdom, these low expulsion rates indicate that previous notions regarding insertion timing may not be accurate. Satisfaction levels were also favourable. PPIUD can be safe, acceptable and feasible in an African setting.

Abstract

The United States Agency for International Development (USAID) estimates that there are 225 million women and girls with unmet contraceptive need yearly. Unmet need for contraception is defined as women who desire a delay in childbearing and are not using a modern method of contraception. It is projected that providing contraception to these women would avert 36 million abortions, 70,000 maternal deaths, and 52 million unintended pregnancies overall. In the past 30 years, there has been an increase both in population and in contraception use in the developing world. As a result, it is estimated that in 2015 there were 500 million contraceptive users in developing countries, which is nearly double the prevalence in 2000. Unfortunately, women and girls in developing nations still face many obstacles in obtaining modern methods of contraception. Particular challenges in the developing world include lack of access due to inadequate number of trained providers, fewer method options, and "stock-outs" of contraceptive supplies. Innovative strategies for decreasing unmet need will have to address these challenges, and will necessarily involve programmatic solutions such as community-based distribution and social marketing campaigns. Additionally, increasing uptake of long-acting reversible contraceptive methods will be essential for achieving the goal of decreasing unmet need.

Abstract

It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3.Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel.There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization.Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries.

Abstract

Cervical cancer is the second most common form of cancer for women in Ethiopia. Using a single-visit approach to prevent cervical cancer, the Addis Tesfa (New Hope) project in Ethiopia tested women with HIV through visual inspection of the cervix with acetic acid wash (VIA) and, if tests results were positive, offered immediate cryotherapy of the precancerous lesion or referral for loop electrosurgical excision procedure (LEEP). The objective of this article is to review screening and treatment outcomes over nearly 4 years of project implementation and to identify lessons learned to improve cervical cancer prevention programs in Ethiopia and other resource-constrained settings.We analyzed aggregate client data from August 2010 to March 2014 to obtain the number of women with HIV who were counseled, screened, and treated, as well as the number of annual follow-up visits made, from the 14 tertiary- and secondary-level health facilities implementing the single-visit approach. A health facility assessment (HFA) was also implemented from August to December 2013 to examine the effects of the single-visit approach on client flow, staff workload, and facility infrastructure 3 years after initiating the approach.Almost all (99%) of the 16,632 women with HIV counseled about the single-visit approach were screened with VIA during the study period; 1,656 (10%) of them tested VIA positive (VIA+) for precancerous lesions. Among those who tested VIA+ and were thus eligible for cryotherapy, 1,481 (97%) received cryotherapy treatment, but only 80 (63%) women eligible for LEEP actually received the treatment. The HFA results showed frequent staff turnover, some shortage of essential supplies, and rooms that were judged by providers to be too small for delivery of cervical cancer prevention services.The high proportions of VIA screening and cryotherapy treatment in the Addis Tesfa project suggest high acceptance of such services by women with HIV and feasibility of implementation in secondary- and tertiary-level health facilities. However, success of cervical cancer prevention programming must address wider health system challenges to ensure sustainability and appropriate scale-up to the general population of Ethiopia and other resource-constrained settings.

Abstract

To assess the feasibility, acceptability, and safety of a dedicated postpartum intrauterine device (PPIUD) inserter specifically designed for the post-delivery setting. Primary objectives of fundal placement and expulsion rates were assessed. Secondary objectives were participant satisfaction and IUD retention.In this pilot proof of concept, we enrolled 80 women who presented for PPIUD insertion at 2 government hospitals in Delhi and Lucknow, India, between March and July 2015. PPIUD insertion was completed with the dedicated inserter in all cases, by trained providers with no prior experience in PPIUD insertion, followed immediately by ultrasound to assess location and fundal placement of the IUD. Follow-up took place at 6 to 8 weeks post-insertion, and ultrasound was used to assess IUD location. Providers and participants also completed satisfaction surveys.High fundal placement (≤10 mm from uterine fundus) was achieved with the dedicated PPIUD inserter in 82% of cases (n = 65). There were no perforations or infections among the participants and no other complications associated with use of the dedicated inserter. The mean distance between the IUD and the endometrial verge immediately post-insertion was 5.8 mm (range, 0-31; N = 80); this distance at follow-up was also 5.8 mm (range, 0-25; n = 50). Complete expulsion was observed in 6 cases (7.5%), and asymptomatic partial expulsion in 8 cases (10%). Providers reported the majority (93%, n = 74) of insertions to be easy. The majority (74%, n = 59) of participants reported the same level of pain before and after insertion.This dedicated PPIUD inserter performed as intended and was found to be safe, with high acceptability among the participants and providers. Further study and use of the dedicated inserter may reveal reduced risk of infection among PPIUD users as well as increased convenience compared with standard PPIUD insertion techniques, and could improve acceptability of postpartum IUD provision among providers. The success of this study has led to the initiation of a formal randomized controlled trial in India to further investigate the acceptability of the dedicated inserter.

Abstract

The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here, we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. We found that human astrocytes have abilities similar to those of murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. Next, we performed RNA sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells (available at http://www.brainrnaseq.org). With these profiles, we identified novel human-specific astrocyte genes and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell-type-specific molecular profiles of the healthy and diseased human brain.

Abstract

Introduction. Cervical cancer is one of the leading causes of cancer death among Ethiopian women. Low awareness of cervical cancer, in combination with low health care seeking behavior, is a key challenge for cervical cancer prevention. This study assessed the knowledge of cervical cancer among HIV-infected women in Ethiopia. Methods. A facility-based cross-sectional survey was conducted from August to September 2012 among HIV-infected women between 21 and 49 years of age. Basic descriptive statistics were performed using SPSS. Results. A total of 432 HIV-infected women participated in this study. About 71% of participants had ever heard of cervical cancer. Among women who had ever heard of cervical cancer, 49% did not know the cause while 74% were able to identify at least one risk factor for cervical cancer. Only 33% of women were able to correctly address when women should seek care and 33% identified at least one treatment option for cervical cancer. Conclusion. This study revealed that knowledge about cervical cancer was generally low, in particular for health care seeking behavior and treatment of cervical cancer. Health awareness programs should be strengthened at both community and health facility levels with emphasis highlighting the causes, risk factors, care seeking behaviors, and treatment options for cervical cancer.

Abstract

To assess whether buccal misoprostol is effective for the treatment of intrauterine fetal death.This double-blind randomized trial was conducted at five tertiary-level hospitals in the United States and Vietnam. One hundred fifty-three women with an intrauterine fetal death at 14-28 weeks of pregnancy received either 100 mcg buccal misoprostol or 200 mcg buccal misoprostol every 6 h for a maximum of 8 doses. The main outcome measure was the fetal-placental delivery rate within 48 hours of prostaglandin commencement without any additional intervention.Most of the women (140/153) were recruited at the study site in Vietnam. Expulsion of both fetus and placenta within 48 hours of prostaglandin commencement without any additional interventions occurred in 61.8% (47/76) of women receiving misoprostol 100 mcg and 77.9% (60/77) of women receiving misoprostol 200 mcg. The 200 mcg dose was significantly more effective than the 100 mcg dose at expelling the fetus and placenta within 48 h [RR 0.68 (95% CI: 0.50-0.92; p=.03)]. The mean time to expulsion was significantly shorter using the 200 mcg dose (18.5±11.9 h) than the 100 mcg dose (23.9±12.5 h) (p=.02). Most women in both groups found the procedure satisfactory or very satisfactory (100 mcg: 76.7% (56/73); 200 mcg: 89.5% (68/76) [RR 0.86 (95% CI: 0.74-1.00)].Buccal misoprostol is an effective method for medical induction of labor after intrauterine fetal demise. A 200 mcg dose is significantly more effective than 100 mcg for evacuating the uterus within 48h. The treatment is highly acceptable to women.Administration of 200 mcg buccal misoprostol every six hours is an effective and acceptable method to effect the delivery of a demised fetus at 14-28 weeks that can be feasibly implemented in a wide variety of settings.

Abstract

To investigate phone follow-up with a semiquantitative urine pregnancy test and symptom checklist as a replacement for universal clinic follow-up after medical abortion.One thousand four hundred thirty-three women seeking early medical abortion at four hospitals in Vietnam were randomized to clinic or phone follow-up. Women allocated to clinic follow-up returned to the hospital for confirmation of abortion outcome 2 weeks after mifepristone administration. Women assigned to phone follow-up completed a semiquantitative pregnancy test at initial visit to determine baseline human chorionic gonadotropin range and again at home 2 weeks later. Clinic staff called women to review the pregnancy test results and symptom checklist. Women who screened positive were referred to the clinic. Effectiveness, feasibility, and acceptability of the follow-up methods were assessed.The rate of ongoing pregnancy was not significantly different between the two groups (clinic: 2.7% phone, 2.5%, relative risk 0.9, 95% confidence interval 0.99-1.02). Eighty-five percent of women in the phone group did not need an additional clinic visit. Phone follow-up was highly effective in screening for ongoing pregnancy with a sensitivity and specificity of 92.8% and 90.6%, respectively. Specificity of the pregnancy test alone (eg, without the symptom checklist) was higher (95.7%).Phone follow-up offers a feasible and effective approach to identify women with ongoing pregnancy after early medical abortion. When used with the semiquantitative pregnancy test, the symptom checklist offered no additional benefit and decreased the specificity of the screening. Given its effectiveness and ease of use, the semiquantitative pregnancy test alone could replace routine clinic follow-up after early medical abortion.ClinicalTrials.gov, www.clinicaltrials.gov, NCT01150422.I.

Abstract

A specially designed inserter aims at facilitating IUD insertion within 10 minutes to 48 hours after delivery during the postpartum period when demand for, and health benefits of, contraception are high.

Abstract

This qualitative study aimed to assess factors influencing pregnant women's decision to seek or avoid antenatal care (ANC) in the Andes of Peru. Open-ended, semi-structured interviews were conducted with 24 women utilizing ANC (+) and 10 women avoiding ANC (-). Interviews were translated to English from Quechua and Spanish, transcribed, and analyzed using grounded theory. Factors influencing ANC- women included: expecting criticism for having additional children; long ANC wait time and inconvenient hours of operation; and masculine gender of health workers. For ANC+ women, motivating factors included: maximizing positive health outcomes; past negative maternity experiences; pressure from family members; and avoidance of rumored fines or fees associated with ANC non-attendance and in-hospital deliveries, respectively. Both ANC+ and ANC- women were fearful and embarrassed about possible criticism for having additional children and the gender of the health workers, yet they weighed these factors differently. To better understand how rural women make decisions about ANC attendance, it is important to consider the value they place on the factors influencing their decision, and their emotional assessment of such issues.

Abstract

The major contraceptive action of the levonorgestrel-releasing intrauterine system (LNG-IUS) is cervical mucus (CM) thickening, which prevents sperm penetration. No study to date has examined the temporal relationship between the insertion of the LNG-IUS and changes in CM quality and sperm penetration.Participants were enrolled in a clinically descriptive study to compare the quality of CM and three parameters of sperm penetration prior to insertion of the LNG-IUS and on Days 1, 3 and 5 after insertion. Measurements of estradiol, progesterone and levonorgestrel (LNG) in serum and LNG in CM were also carried out at these times. CM was analyzed using the World Health Organization CM grading criteria. Sperm penetration was determined using an in vitro sperm-CM penetration test.All 10 participants underwent LNG-IUS insertion during midcycle when CM quality was good and sperm penetration was excellent. On Day 1 after LNG-IUS insertion, the majority of participants demonstrated poor CM quality and poor sperm penetration. On Day 3, all participants had poor CM quality, and all but one subject had poor sperm penetration. By Day 5, all participants had poor CM quality and poor sperm penetration. LNG levels in CM peaked on the day after LNG-IUS insertion.Significant changes in quality of CM and sperm penetration were observed shortly after LNG-IUS insertion; however, CM can remain penetrable for up to 5 days when the LNG-IUS is inserted midcycle.

Abstract

The effect of combined oral contraceptives (COCs) and depot-medroxyprogesterone acetate (DMPA) on the area of cervical ectopy is not well understood.From 1996 to 1999, we recruited women not using hormonal contraception from two family planning centers in Baltimore, MD. Upon study entry and 3, 6 and 12 months after the initial visit, participants were interviewed and received visual cervical examinations with photography. Ectopy was measured from digitized photographs and was analyzed both continuously and categorically (small [≤0.48 cm(2)] vs. large [>0.48 cm(2)]).Of 1003 enrolled women, 802 returned for at least one follow-up visit. At 12 months, the numbers of women using COCs, DMPA or no hormonal method at least 50% of the time since the prior visit were 230, 76 and 229, respectively. After multivariable adjustment, COC use (vs. no hormonal use) was associated with large area of ectopy (odds ratio [OR]: 1.8, 95% confidence interval [CI]: 1.0-3.3). No significant relationship was observed between DMPA and large area of ectopy (OR: 0.5, 95% CI: 0.2-1.3). The incidence of large area of ectopy by contraceptive exposure (COC, DMPA or no hormonal method) was 17.4 (CI: 11.8-24.6), 10.9 (CI: 4.4-22.4) and 4.6 (CI: 2.2-8.4) per 100 woman-years, respectively.Use of COCs, but not DMPA, was associated with large area of cervical ectopy. Area of ectopy at baseline was the strongest predictor of area of ectopy at follow-up.

Abstract

To review the literature for economic and health-related quality of life outcomes data associated with the use of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the management of heavy menstrual bleeding.We searched the MEDLINE and EMBASE databases simultaneously using the Ovid interface to review the literature in a systematic manner for economic and health-related quality of life outcomes data associated with the use of the LNG-IUS in women with heavy menstrual bleeding. Articles were then selected for further review based on the relevance of their titles and/or abstracts. We identified 17 articles for inclusion in this review.Treating heavy menstrual bleeding with the LNG-IUS was found to be cost-effective in various countries and settings. Moreover, irrespective of the measuring instrument used, health-related quality-of-life outcomes were found to be improved to a degree similar to that achieved with endometrial ablation or hysterectomy. In some cases, the LNG-IUS appeared to be more effective and less costly than the surgical options.The LNG-IUS is a cost-effective treatment option for heavy menstrual bleeding when pharmacologic treatment is indicated.

Abstract

Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). Unlike embryonic stem cells, virtually little is known regarding the factors that regulate EGC survival and maintenance. In mice, the growth factor bone morphogenetic protein 4 (BMP4) has been shown to be required for maintaining mouse embryonic stem cells, and disruptions in this gene lead to defects in mouse PGC specification. Here, we sought to determine whether recombinant human BMP4 could influence EGC derivation and/or human PGC survival. We found that the addition of recombinant BMP4 increased the number of human PGCs after 1 week of culture in a dose-responsive manner. The efficiency of EGC derivation and maintenance in culture was also enhanced by the presence of recombinant BMP4 based on alkaline phosphatase and OCT4 staining. In addition, an antagonist of the BMP4 pathway, Noggin, decreased PGC proliferation and led to an increase in cystic embryoid body formation. Quantitative real-time (qRT)-polymerase chain reaction analyses and immunostaining confirmed that the constituents of the BMP4 pathway were upregulated in EGCs versus PGCs. Downstream activators of the BMP4 pathway such as ID1 and phosphorylated SMADs 1 and 5 were also expressed, suggesting a role of this growth factor in EGC pluripotency.

Abstract

Women's primary-care services are frequently dispensed to HIV-infected women through HIV specialty clinics. Our objective was to evaluate cervical cancer and breast cancer screening practices in a county-based HIV clinic in San Mateo, California.This was a retrospective cohort study of medical records of HIV-infected women obtaining HIV care at this site.Between January 1, 2002 and December 31, 2006, 69 women were documented to have at least 12 months of medical care at the clinic. Median followup time was 51 months. Over 253 person-years of followup, there were 656 pap smears performed per 1,000 person-years; 77.9% of women had at least one Pap smear during the study time period. A total of 59.5% (47/79) of normal pap smears had a followup pap smear within 18 months; 62.0% of abnormal pap smears had a followup pap smear within 12 months. A CD4 count of less than 200 cells/mm(3) was associated with not receiving a pap smear in multivariable analysis. Mammogram screening was performed on 64.7% of women aged 40 or older.Based on the results of this study, the majority of HIV-infected women at this clinic received cervical and breast cancer screening at some point during their care. Only two-thirds of abnormal pap smear results had followup pap smear screening within a year. With the increased risk of cervical cancer in HIV-infected women, efforts should be made to promote cervical cancer screening, particularly in high-risk women.

Abstract

To assess the effect of introducing visual inspection with acetic acid and cryotherapy on cervical cancer incidence rates in Roi Et province over time, between 1997 and 2006, and compare this with two nearby provinces.Data from two cancer registration units, one in Srinagarind Hospital and another in Ubon Ratchathani Cancer Center (to which all cervical cancer patients were referred from the three study provinces) were registered, extracted, combined and analyzed using a generalized estimation equation.Cervical cancer detection rates improved. These are represented by the apparent increased incidence rates in Roi Et province during the study period compared with two nearby provinces (P = 0.01), equivalent to a doubling of the previously reported age-standardized incidence ratio and three times its baseline in 2006.A single-visit approach to cervical cancer prevention in Roi Et province using visual inspection with acetic acid and cryotherapy appeared to have an effect in revealing an increased cervical cancer incidence rate by achieving higher coverage, resulting in increased case finding.

Abstract

To compare the clearance rate of HPV infection among women aged older than 30 years with biopsy-confirmed cervical low-grade squamous intraepithelial lesions (LSIL) 1 year after cryotherapy with the spontaneous clearance rate (observation).HPV DNA typing by polymerase chain reaction and reverse line blot hybridization were used to identify 14 high-risk types and 23 low-risk types. HPV DNA sequencing was also used for other types.Between December 2007 and March 2009, 100 women were recruited to the study and 60 cases had positive results on HPV testing. Twenty-nine patients were randomly allocated to the cryotherapy group and 31 to the observation group. At 1 year, 89.7% (26/29; 95% CI, 78.6-100%) of the cryotherapy group and 90.3% (28/31; 95% CI, 79.9-100%) of the observation group had negative results on HPV testing (0.6% difference; 95% CI, -15.8 to 14.6%, P=0.94).Cryotherapy failed to increase the clearance of prevalent HPV infections among women with LSIL, although in both arms the clearance rates were above 80%. However, in coupling with visual inspection with acetic acid as a single visit approach, its effect on prevention of HSIL and cervical cancer is still promising. Therefore, cryotherapy should not be withdrawn from such programs.

Abstract

This study aimed to compare digital camera assessment of the reproductive tract (DART) to colposcopy for the evaluation of abnormal Pap smears.Participants included 207 women with abnormal Pap smears. Colposcopy and DART were performed on each patient by separate examiners with the goal of lesion detection. Analysis was performed per patient and per biopsy.Patients had an average of 2.9 biopsies. Forty-two patients and 81 biopsies were positive for cervical intraepithelial neoplasia 2+. Both DART and colposcopy detected 41 (97.6%) of 42 patients (95% CI = 85.9%-99.9%). Digital camera assessment of the reproductive tract detected 66/81 (81.4%; CI = 70.7%-88.9%) and colposcopy detected 69/81 (85.2%; CI = 73.2%-92.4%) of biopsies that were cervical intraepithelial neoplasia 2+.Digital camera assessment of the reproductive tract detects high-grade lesions of the cervix with similar sensitivity to colposcopy. It holds great promise to expand cervical cancer precursor lesion detection in areas with limited resources.

Abstract

To assess which of the 5 CareHPV-inclusive protocols stakeholders in Roi-et Province, Thailand found (1) most preferable and (2) most beneficial to the overall goal of reducing cervical cancer.Five CareHPV-inclusive cancer prevention approaches were presented to a convenience sample of colposcopists, trainers, health care providers, district medical directors, and district health officers. Participants ranked their preference for each plan (A-E) compared with the current screening protocol and also the perceived comparative benefit of the plans. Plans differed in whether every patient was screened using both the human papillomavirus (HPV) test and visual inspection with acetic acid (VIA) or only HPV-positive women were screened with VIA; in clinician versus self-swab and in hospital/clinic-based or village-based screening.Overall, participants supported an innovative plan in which women would be screened in their homes and villages using the self-swab version of the CareHPV DNA test, and only those who screened positive for HPV are screened with VIA. When results were stratified by provider type (physician vs nonphysician) and/or practice concentration (hospital-oriented vs field-oriented), preference and perceived benefit for the plans differed significantly with physician/hospital-oriented participants and are more likely to be skeptical of the self-swab version of the CareHPV test.Providers in Thailand recognize the potential value of a rapid HPV test as part of a cervical cancer prevention program and, overall, support a patient-administered self-swab followed by visual confirmation and treatment as the most practical CareHPV-inclusive approach largely because of the likely increase in coverage. Future studies will further define the clinical benefits and limitations of this test.

Abstract

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a safe, effective and acceptable form of contraception used by over 150 million women worldwide. It also has a variety of noncontraceptive benefits including treatment for menorrhagia, endometriosis, and endometrial hyperplasia. The LNG-IUS has also been used in combination with estrogen for hormone replacement therapy and as an alternative to hysterectomy. Overall, the system is very well tolerated and patient satisfaction is quite high when proper education regarding possible side effects is provided. However, despite all of the obvious benefits of the LNG-IUS, utilization rates remain quite low in the developed countries, especially in the United States. This is thought to be largely secondary to the persistent negative impressions from the Dalkon Shield intrauterine experience in the 1970s. This history continues to negatively influence the opinions of both patients and health care providers with regards to intrauterine devices. Providers should resolve to educate themselves and their patients on the current indications and uses for this device, as it, and intrauterine contraception in general, remains a largely underutilized approach to a variety of women's health issues.

Abstract

This study was conducted to compare the safety, effectiveness and acceptability of 400 mcg sublingual misoprostol and 600 mcg oral misoprostol for treatment of incomplete abortion.We used an open-label randomized controlled trial conducted from July 2005 to August 2006 in a large tertiary level maternity hospital in Antananarivo, Madagascar, and a large tertiary level hospital in Chisinau, Moldova. Three hundred consenting women seeking treatment for clinically diagnosed incomplete abortion with uterine size

Abstract

Hormonal contraceptives have been a part of clinical practice for more than 40 years, and family planning programs, based largely on contraceptive provision, are regarded as one of the most successful public health interventions of the 20th century. Thus, discussion of family planning issues and contraceptive considerations has become an integral component of women's health care and one of the benchmarks of the traditional annual well-women visit. In terms of cost-effectiveness, prevention of unplanned pregnancies through contraceptive use has repeatedly been shown to be a highly cost-effective use of health care dollars. Options for effective hormonal contraception have expanded tremendously and include a variety of delivery options, including the pills both in traditional 21/7 format, and more recently in a 24/4 format, as well as a vaginal ring, a skin patch, implants, and the hormonally medicated intrauterine device. Importantly, the overall risks associated with hormonal contraceptives have been reduced as compared with older formulations, even for women with medical conditions. Many modern hormonal contraceptives also offer valuable noncontraceptive benefits. To help clinical decision making, a number of evidence-based guides have been published, and the American College of Obstetricians and Gynecologists has recently updated their practice bulletin on contraception use in women with medical conditions. In general, clinical protocols for provision of hormonal contraceptives have been streamlined, and unnecessary practices, tests, and procedures are identified and discouraged. In this review, we will summarize both technical and programmatic aspects of hormonal contraceptive use, and methods are discussed in order of efficacy from highest to lowest.

Abstract

The aim of the study was to evaluate pain and predictors of pain in women undergoing electric (EVA) or manual vacuum aspiration (MVA) for first trimester surgical abortions and to examine how perceptions of pain differ among participants, advocates (participant support person) and physicians.In this randomized controlled study, women presenting for first trimester abortion underwent standardized EVA or MVA. Participants completed questionnaires, visual analog scales (VAS) and Likert scales for pain. Logistic and linear regression models were used to analyze the data.Nonwhite women and women who preoperatively expected more pain reported higher procedure-related pain scores. Vacuum source, previous history of abortion, comfort with decision to have an abortion and partner involvement did not affect participant pain scores. In the multivariable analyses, no single factor predicted procedure-associated pain. The advocates perceived that more educated women had less pain. Physicians felt longer procedures and a woman's fear of pelvic examinations caused more pain. Physicians believed women had less pain than the participants reported themselves (p

Abstract

Second trimester abortion is associated with higher rates of complications compared to first trimester abortion. Dilatation and evacuation (D&E) and medical induction using misoprostol alone or a combination of mifepristone and misoprostol are the methods most commonly used for later abortion in developed countries, yet little research has directly compared them. We reviewed the literature on PubMed and identified only one small randomised controlled trial and one retrospective cohort study with comparative data for these methods, although the cohort study did not include cases using the mifepristone regimen. We expanded our search to include case series and cohort studies for a single method. In the randomised trial, women undergoing medical induction reported significantly more pain and experienced more adverse events. In the cohort study, incomplete abortion was significantly more common among women undergoing medical induction. In the single method studies, serious complications such as uterine perforation, uterine rupture and haemorrhage were rare, although the latter may be more common with medical induction. Mild infection may also be more prevalent after medical induction. Current evidence suggests that, given trained providers and where otherwise feasible, D&E is preferable to medical induction. A larger randomised controlled trial is needed that directly compares outcomes between the two methods, examines acceptability to women and explores clinicians' perspectives on providing them.

Abstract

Human primordial germ cells (PGCs) can give rise to pluripotent stem cells such as embryonal carcinoma cells (ECCs) and embryonic germ cells (EGCs).In order to determine whether PGCs express markers associated with pluripotency in EGCs and ECCs, the following study cross examines the expression patterns of multiple pluripotent markers in the human fetal ovary, 5.5-15 weeks post-fertilizaton (pF) and relates this expression with the ability to derive pluripotent EGCs in vitro.Specific subpopulations were identified which included OCT4(+)/Nanog(+)/cKIT(+)/VASA(+) PGCs and oogonia. Interestingly, these cells also expressed SSEA1 and alkaline phosphatase (AP) and SSEA4 expression occurred throughout the entire gonad. Isolation of SSEA1(+) cells from the gonad resulted in AP(+) EGC colony formation. The number of OCT4(+) or Nanog(+) expressing cells peaked by week 8 and then diminished after week 9 pF, as oogonia enter meiosis. In addition, the efficiency of EGC derivation was associated with the number of OCT4(+) cells. TRA-1-60 and TRA-1-81 were only detected in the lining of the mesonephric ducts and occasionally in the gonad.These results demonstrate that PGCs, a unipotent cell, express most, but not all, of the markers associated with pluripotent cells in the human fetal ovary.

Abstract

Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). However, the developmental potency of these cells in the fetal gonad still remains elusive. Thus, this study provides a comprehensive analysis of pluripotent and germ cell marker expression in human fetal testis 7-15 weeks postfertilization (pF) and compares this expression to their ability to derive EGCs. Although the majority of germ cells expressed stem cell markers stage-specific embryonic antigen (SSEA) 1, SSEA4, EMA-1, and alkaline phosphatase, only a small percentage of those (<1%) expressed OCT4, CKIT, and NANOG. Specifically, the number of OCT4(+)/CKIT(+)/NANOG(+) cells significantly increased in the developing cords during weeks 7-9, followed by a gradual decline into week 15 pF. By week 15 pF, the remaining OCT4(+)/CKIT(+)/NANOG(+) cells were found in the cords surrounding the periphery of the testis, and the predominant germ cells, CKIT(+) cells, no longer expressed OCT4 or NANOG. Based on morphology and early germ cell marker expression, including VASA, PUM2, and DAZL, we suggest these cells are mitotically active gonocytes or prespermatogonia. Importantly, the number of OCT4(+) cells correlated with an increase in the number of EGC colonies derived in culture. Interestingly, two pluripotent markers, Tra-1-60 and Tra-1-81, although highly expressed in EGCs, were not expressed by PGCs in the gonad. Together, these results suggest that PGCs maintain expression of pluripotent stem cell markers during and after sexual differentiation of the gonad, albeit in very low numbers.

Abstract

To evaluate the tolerability and clinical safety of the subdermal, long-acting hormonal contraceptive Implanon.This integrated safety analysis included 11 international studies concerning Implanon (68 mg etonogestrel) of which 10 had a duration of at least two years. Assessments included reports of adverse events (AEs), reasons and rates of discontinuation, insertion/removal complications, and the condition of the implant site. Metabolic and coagulation parameters are briefly discussed to fully describe the clinical safety profile.In total 942 women were exposed to Implanon for 24,679 cycles over the course of one to five years. The overall discontinuation rate was 32.7%; the most frequently reported reasons for discontinuation were adverse events (13.9%), bleeding irregularities (10.4%), and planning pregnancy (4.1%). The most commonly reported drug-related AE was headache (15.3%); however, headache was reported in only 1.6% of women as a reason for discontinuation. Insertion and removal times for Implanon were short with few complications, none of which were major. From earlier studies it is known that treatment with Implanon has little effect on metabolic and coagulation parameters.Implanon is a well-tolerated and safe method of long-acting hormonal contraception for women.

Abstract

Verification bias occurs when the percentage of subjects receiving disease verification differs according to the test result. Statistical adjustment yields unbiased sensitivity and specificity under a missing at random (MAR) assumption.To use an example from an international study to show how the assumptions needed for unbiased statistical adjustment for verification bias can be undermined by conditions on the ground, and that accuracy of estimates is also compromised by too low a sampling fraction of subjects who test negative.A study in Zimbabwe assessed the accuracy of a screening test for cervical cancer screening, visual inspection with acetic acid (VIA). The study was conducted in two phases, Phase I, where only 10% of subjects with negative tests received verification, and Phase II, in which nearly all subjects were verified. Unadjusted, simple- and covariate-adjusted estimates were compared to investigate factors affecting differences. Bootstrap simulations were used to illustrate the effect of varying test negative sampling fractions.Phase I unadjusted sensitivity and specificity were 0.66 (0.61-0.70) and 0.34 (0.31-0.36), respectively. Simple-weighted adjusted estimators accounting only for VIA status were 0.20 (0.17-0.23) and 0.80 (0.78-0.81), respectively, suggesting the test to be useless. It was found that verification (colposcopy) capacity in-country had been exceeded, and that random selection of test negative patients for colposcopy had been compromised. Phase II estimates of sensitivity and specificity were 0.77 and 0.64, respectively. With 9% disease prevalence, a VIA test-negative sampling fraction >50% was necessary for the confidence intervals for sensitivity to have more than a 90% probability of including the true value.Phase I statistical adjustment was not made for MAR deviations unexplained by the two auxiliary factors, Pap results and STD history. Adjustment was not possible for other unmeasured co-factors.While there are standard formulae for correcting for verification bias, these will be biased if the MAR assumption is not met, which can occur through the actions of study personnel or subjects. Design of such studies in low resource environments needs to either require 100% verification, or employ procedures ensuring that the sample of test negatives who receive verification is indeed random. In addition, required test negative sampling fractions need to incorporate information on both disease prevalence and overall sample size.

Abstract

A combination of mifepristone and misoprostol is the regimen of choice for termination of pregnancy between 13 to 26 weeks. In many countries, mifepristone is still not available, and misoprostol has to be used alone. Many misoprostol-alone regimens have been reported in the literature with apparently good results. Most of the trials were conducted in pregnancies between 13 and 22 weeks. For this gestational period, we recommend the regimen of 400 microg of vaginal misoprostol every 3 h up to 5 doses, as it appears to be effective without excessive side effects or complications. There is inadequate data to recommend a regimen for the gestational period of 23 to 26 weeks but it is advisable to reduce the dose and frequency of administration of misoprostol. Common side effects of misoprostol-induced termination of pregnancy include gastrointestinal side effects, abdominal cramps, bleeding, fever and chills. Complications may include infection or rarely rupture of uterus.

Abstract

The purpose of this study was to validate the accuracy of an alternative cervical cancer test - visual inspection with acetic acid (VIA) - by addressing possible imperfections in the gold standard through latent class analysis (LCA). The data were originally collected at peri-urban health clinics in Zimbabwe.Conventional accuracy (sensitivity/specificity) estimates for VIA and two other screening tests using colposcopy/biopsy as the reference standard were compared to LCA estimates based on results from all four tests. For conventional analysis, negative colposcopy was accepted as a negative outcome when biopsy was not available as the reference standard. With LCA, local dependencies between tests were handled through adding direct effect parameters or additional latent classes to the model.Two models yielded good fit to the data, a 2-class model with two adjustments and a 3-class model with one adjustment. The definition of latent disease associated with the latter was more stringent, backed by three of the four tests. Under that model, sensitivity for VIA (abnormal+) was 0.74 compared to 0.78 with conventional analyses. Specificity was 0.639 versus 0.568, respectively. By contrast, the LCA-derived sensitivity for colposcopy/biopsy was 0.63.VIA sensitivity and specificity with the 3-class LCA model were within the range of published data and relatively consistent with conventional analyses, thus validating the original assessment of test accuracy. LCA probably yielded more likely estimates of the true accuracy than did conventional analysis with in-country colposcopy/biopsy as the reference standard. Colposcopy with biopsy can be problematic as a study reference standard and LCA offers the possibility of obtaining estimates adjusted for referent imperfections.

Abstract

Abnormal uterine bleeding (AUB) impacts women's health-related quality of life (HRQoL) and puts a heavy economic burden on society. To date, this burden has not been systematically studied. We conducted a systematic review of the medical literature to evaluate the impact of AUB on HRQoL and to quantify the economic burden of AUB from a societal perspective.We searched the PubMed and Cochrane databases, and article bibliographies for the period up to July 2005. Teams of two reviewers independently abstracted data from studies that reported outcomes of interest: prevalence, HRQoL, work impairment, and health-care utilization and costs associated with AUB.The search yielded 1009 English-language articles. Ninety-eight studies (including randomized controlled trials, observational studies, and reviews) that met the inclusion and exclusion criteria underwent a full-text review. The prevalence of AUB among women of reproductive age ranged from 10% to 30%. The HRQoL scores from the 36-item Short-Form Health Survey Questionnaire (SF-36) suggested that women with AUB have HRQoL below the 25th percentile of that for the general female population within a similar age range. The conservatively estimated annual direct and indirect economic costs of AUB were approximately $1 billion and $12 billion, respectively. These figures do not account for intangible costs and productivity loss due to presenteeism.The burden of AUB needs further and more thorough investigation. Additional research should prospectively evaluate the impact of AUB and the value of treatment provided to help guide future health resource allocation and clinical decision-making.

Abstract

The Millennium Development Goals (MDGs), committed to by all 191 United Nations member states, are rooted in the concept of sustainable development. Although 2007 (midway) reports indicated that programs are under way, unfortunately many countries are unlikely to reach their goals by 2015 due to high levels of poverty. Madagascar is one such example, although some gains are being made. Attempts of this island nation to achieve its MDGs, expressed most recently in the form of a Madagascar Action Plan, are notable in their emphasis on (1) conserving the country's natural resource base, (2) the effect of demographic trends on development, and (3) the importance of health as a prerequisite for development. Leadership in the country's struggle for economic growth comes from the president of the Republic, in part, through his "Madagascar Naturally" vision as well as his commitment to universal access to family planning, among other health and development interventions. However, for resource-limited countries, such as Madagascar, to get or stay "on track" to achieving the MDGs will require support from many sides. "Madagascar cannot do it alone and should not do it alone." This position is inherent in the eighth MDG: "Develop a global partnership for development." Apparently, it takes a village after all - a global one.

Abstract

This study aims to compare the cost-effectiveness of oral contraceptives (OCs), the levonorgestrel-releasing intrauterine system (LNG-IUS) and surgical management in treating dysfunctional uterine bleeding (DUB) in women not desiring additional children.A Markov model was constructed from the perspective of the health services payers for a 5-year period. Treatment costs, DUB treatment success rates and contraception success rates were obtained through a literature review.In women not responding to an initial trial of OCs, surgical management was more effective than the LNG-IUS (95.5% vs. 92%) but at higher cost (US$4853 vs. US$2796 per woman). Among responders to OCs, continuing treatment with the LNG-IUS instead of OCs was more effective (92% vs. 90.4%) and less expensive (US$2796 vs. US$4711). For women naïve to medical therapy, the LNG-IUS and OCs had similar effectiveness, but cost for the LNG-IUS was lower (US$2796 vs. US$4895). In all scenarios, surgery followed if medical therapy failed; rates of primary method failure were 62.5% with OCs and 34% with the LNG-IUS at 12 months.Treatment strategies employing the LNG-IUS are the most cost-effective in managing DUB, regardless of whether a woman has previously tried OC therapy.

Abstract

To examine factors associated with postpartum contraception, including the relationship between ethnicity and postpartum contraceptive use.We used data from the New Mexico Pregnancy Risk Assessment Monitoring System, which monitors selected maternal events occurring before, during and after pregnancy.Our findings in 4096 women revealed that women who are aged >or=35 years, unmarried and lacking a postpartum visit have increased risk of no postpartum contraception. The odds of postpartum contraception were over three times greater in women with a postpartum visit [adjusted odds ratio (OR)=3.06, 95% confidence interval (CI): 2.17-4.31) and over 50% greater in married women (adjusted OR=1.57, 95% CI: 1.16-2.11). Hispanic women were more likely than were Native Americans to use postpartum contraception (OR=1.25, 95% CI: 0.95-1.64).Focused contraception counseling, especially in the postpartum setting, is important to help ensure the well-being of women and children.

Abstract

The modern approach to cervical cancer prevention, characterized by use of cytology and multiple visits for diagnosis and treatment, has frequently proven challenging and unworkable in low-resource settings. Because of this, the Alliance for Cervical Cancer Prevention (ACCP) has made it a priority to investigate and assess alternative approaches, particularly the use of visual screening methods, such as visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI), for precancer and cancer detection and the use of cryotherapy as a precancer treatment method. As a result of ACCP experience in providing training to nurses and doctors in these techniques, it is now widely agreed that training should be competency based, combining both didactic and hands-on approaches, and should be done in a clinical setting that resembles the service-delivery conditions at the program site. This article reviews ACCP experiences and perceptions about the essentials of training in visual inspection and cryotherapy and presents some lessons learned with regard to training in these techniques in low-resource settings.

Abstract

To provide evidence regarding the safety, efficacy, and acceptability of 200 mg mifepristone followed by home administration of 400 mug oral misoprostolThe 376 women enrolled in this prospective, open-label, multicenter trial were administered mifepristone in the clinic and were given 2 tablets of 200 mug misoprostol to swallow at home 48 hours later. On day 15, women returned to the clinic for a gynecologic examination. Success was defined as a complete termination without surgical intervention or additional misoprostol by day 21. All participants completed an exit interview before discharge from the studyOf the women enrolled, 58.8% had gestations of between 43 and 49 days, 54.7% had had a previous abortion, and 76% had had a previous pregnancy. Of the 354 women included in the efficacy analysis, 324 (91.5%) had a successful termination. The most common adverse effects reported by patients were pain or cramps (93.2%) and nausea (66.6%), followed by weakness (54.7%), headache (46.2%), and dizziness (44.4%). Overall acceptability of the regimen was high, with 63.3% of women reporting that it was very satisfactory and an additional 23% reporting that it was satisfactoryA regimen of 200 mg mifepristone followed in 48 hours by home administration of 400 mug oral misoprostol is effective, associated with rare severe adverse effects or adverse events, and acceptable for women seeking medical abortion of pregnancies of up to 49 days duration as compared with the regimen currently approved by the Food and Drug Administration.III.

Abstract

As the AIDS epidemic grows through heterosexual transmission, the development of women-controlled methods for defence against sexually transmitted infections and HIV, such as vaginally applied microbicides, is increasingly important. As part of the evaluation of the safety of all new topical microbicides, an evaluation of the cervix and vagina for any physical or mechanical effects of a potential agent is imperative. Traditionally, colposcopy has been used for such an evaluation. We introduce the concept of using a digital camera to assess the reproductive tract as a practical and effective means for studying the effects of microbicides on the vaginal and cervical epithelium. As much research on microbicides will be undertaken in areas with limited resources, digital assessment of the reproductive tract offers the advantage of portability, ease of use, durability, and accessibility. In addition, it allows digital data storage that can be used to review images, allow quality control, and provide an effective means to compare changes over time.

Abstract

The toxic effects of topical microbicides might include epithelial disruption, and if sufficiently severe, may cause visible bleeding. We have developed two sensitive methods to detect hemorrhage far below the visual detection threshold: an enzyme-linked immunosorbent assay for human hemoglobin and a method for staining and enumerating red blood cells by fluorescent microscopy. We have applied these methods to cervicovaginal and introital lavages, and found them to be sensitive and quantitative over a broad range. Comparing the new techniques with a standard heme-detection assay (Hemastix) we found them to be more sensitive, more objective, more fully quantitative, and more likely to be indicative of recent events. In pilot studies we found that the red blood cell and hemoglobin concentrations in samples taken in the luteal phase of the menstrual cycle are low, but still within the detection range of the new assays, providing a quantifiable baseline from which increases in blood from epithelial disruption can be detected and quantified. We propose that these new methods may be used for the safety assessment of microbicides by detecting and quantifying microhemorrhage in cervicovaginal secretions before and after exposure to microbicide.

Abstract

Several previous studies have suggested that hormonal contraception could be associated with increased risk of cervical infections. However, few high-quality prospective studies have examined this relationship.The goal of this study was to measure the effect of oral contraceptives (OC) and depot-medroxyprogesterone acetate (DMPA) on the acquisition of cervical chlamydial and gonococcal infections.Women attending 2 reproductive health centers in Baltimore, MD, were enrolled into a prospective cohort study. Participants were 15 to 45 years and were initiating OCs or DMPA or not using hormonal contraception. Interviews, physical examinations, and testing for incident cervical infections were conducted at 3, 6, and 12 months.The analysis included 819 women. Most were single (77%) and nulliparous (75%); 43% were black. Median age was 22 years. During the study, 45 women acquired a chlamydial or gonococcal infection (6.2 per 100 women-years). DMPA use (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.5), but not OC use (HR, 1.5; 95% CI, 0.6-3.5), was significantly associated with increased acquisition of cervical infections after adjusting for other risk factors. Cervical ectopy was not an important mediator of cervical infection risk.DMPA use, but not OC use, appeared to be significantly associated with increased acquisition of cervical chlamydial and gonococcal infections.

Abstract

About half of the 1.2 million abortions each year in the United States are repeat abortions. While most abortion providers counsel women about contraception, one reason for the high repeat rate could be failure to take into account the social context of the women--in particular, the male partner. To assess whether there might be a window of opportunity for a contraceptive intervention that includes the male partner at the time of the abortion, we undertook a pilot study at an urban abortion clinic to examine the role of the male partner among women receiving abortions. Between May 2001 and August 2002, two questionnaires were administered to 109 women receiving abortions in a Baltimore City clinic. On the procedure day, women were more likely to be accompanied by a male partner upon arrival (30%) or when leaving (34%) than by any other individual. The majority of women receiving abortions reported that their partners played positive decision-making and support roles throughout the abortion process. A significant proportion of couples could be available for contraceptive counseling following an abortion, providing rationale for couples' post-abortion contraceptive counseling for women whose partners are already actively and positively involved in the abortion process. Such an intervention may help to reduce repeat abortions.

Abstract

A recent review article by Smith et al. in The Lancet purports to find a causal relationship between long-term use of oral contraceptives (OCs) and cervical cancer. While we endorse the search for such a relationship, we felt it important to critically examine Smith et al.'s review process and, as a result, we have questions about the validity of their conclusions. In our view, the findings of published articles as presented by Smith et al. do not confirm a causal connection between long-term use of OCs and cervical cancer. Our goal is not to conduct another formal review of the evidence, but to evaluate whether Smith et al. have met the burden of proof for establishing a causal relationship. Given the importance of OCs to women the world over, we urge reproductive health professionals to consider this issue carefully before accepting that a causal relationship exists.

Abstract

To compare manual and electric vacuum aspiration for surgical abortions between 14 and 18 weeks of pregnancy.A consecutive case series of pregnant women presenting to Johns Hopkins Bayview Medical Center for abortion. There were 73 women in the manual vacuum aspiration group and 37 women in the electric vacuum aspiration group. Dilatation and evacuation was performed using manual or electric vacuum aspiration according to protocol. Procedure time was assessed with the t-test.In all cases, abortion was performed with initial vacuum. Group sizes were sufficient to detect a 20% difference in mean procedure time with 80% power (calculated with two separate S.D.s for procedure time). There was no significant difference in procedure time between the two groups.Manual vacuum aspiration can be safely and effectively used in second-trimester abortion procedures and should be more widely investigated for this purpose.

Abstract

Developing countries often lack the necessary resources to use the Papanicolaou (Pap) smear as a screening tool for cervical abnormalities. Because the burden of cervical cancer is highest in such low-resource settings, alternative techniques have been sought. Recently, interest in visual inspection with acetic acid (VIA) has increased. Numerous studies have been conducted on its accuracy and its ability to detect cervical lesions when compared with other techniques, both conventional and nonconventional. This review summarizes key findings from the literature to provide researchers and policymakers with an up-to-date summary on VIA. PubMed was used to identify relevant journal articles published between 1982 and 2002. Key words were cervical cancer screening, visual inspection, VIA (visual inspection with acetic acid), DVI (direct visual inspection), AAT (acetic acid test), and cervicoscopy. Studies were eligible for review only if they involved analysis of primary VIA data (ie, not review articles); studies involving magnification devices were excluded. Fifteen studies were reviewed in total; key results were extracted and a summary analysis was performed for sensitivity and specificity parameters. When reported, sensitivity ranged between 66% and 96% and specificity between 64% and 98%. Authors comparing VIA with cytology noted that the overall usefulness of VIA compares favorably with that of the Pap test. The reported findings reviewed here suggest that VIA has the potential to be a cervical cancer screening tool, especially in low resource settings.Obstetricians & Gynecologists, Family Physicians.After completion of this article, the reader will be able to describe how visual inspection of the cervix for cervical cancer screening (VIA) is performed, to summarize the current literature on VIA, and to list potential advantages of VIA.

Abstract

This paper examines women's acceptability of and experiences with manual vacuum aspiration (MVA) as compared with electric vacuum aspiration (EVA) for first trimester abortion. Women requesting pregnancy terminations were randomly assigned to either MVA (n = 64) or EVA (n = 63). Participants completed questionnaires before and after their abortions and approximately 2-4 weeks later. We observed some differences by group in participants' ratings of the importance of method characteristics and in their perceptions of their abortion methods after their abortions. The two groups did not, however, differ in their reports of pain, anxiety or bleeding or in the acceptability of their method.

Abstract

Several studies have shown impressive sensitivity and specificity of visual inspection using acetic acid wash (VIA) in detecting cervical dysplasia. This study examines how risk-factor based triage, using clinical history-taking to limit the testing to those at highest risk of disease, improves the clinical utility of VIA.The study population included 2206 woman aged 25-56 from peri-urban primary care clinics in Zimbabwe. Three risk factors variables [age, lifetime number of sexual partners and history of a sexually transmitted infection (STI)] were selected as the basis for computer-simulated patient triage. Criteria for selecting risk factors were biological relevance, programmatic feasibility, historical evidence in the scientific literature as a risk factor for cervical cancer and a significant (P<0.05) predictor of dysplasia in this study population. Predictive values for VIA were calculated on subgroups of women with combinations of the three risk factors and then compared with the predictive value of VIA calculated on the full study population.The positive predictive value (PPV) among women with all three risk factors (30.2%) was 1.6 times higher than that of all study women and 4.5 times higher than women with none of the three risk factors (4.1%). Additionally, the PPV was slightly (30%) higher than that obtained from computer-simulated serial testing using VIA as the primary test followed by HPV testing (27.4%).Clinical history-taking could provide the basis for patient triage to increase the clinical utility of VIA. Such an approach could also serve to prioritize who gets tested first in low-resource countries with high disease prevalence that are struggling to strengthen national cervical cancer prevention programs.

Abstract

About 80% of cervical cancers occur in less-developed countries. This disproportionate burden of cervical cancer in such countries is due mainly to the lack of well-organized screening programs. Several cervical cancer screening strategies have been proposed as more cost-effective than cytology screening. We compared the costs and benefits of different strategies and their effectiveness in saving lives in a less-developed country.We used a population-based simulation model to evaluate the incremental societal costs and benefits in Thailand of seven screening techniques, including visual inspection of the cervix after applying acetic acid (VIA), human papillomavirus (HPV) testing, Pap smear, and combinations of screening tests, and examined the discounted costs per year of life saved (LYS).Compared with no (i.e., not well-organized) screening, all strategies saved lives, at costs ranging from 121 US dollars to 6720 US dollars per LYS, and reduced mortality, by up to 58%. Comparing each strategy with the next least expensive alternative, VIA performed at 5-year intervals in women of ages 35-55 with immediate treatment if abnormalities are found was the least expensive option and saved the greatest number of lives, with a cost of 517 US dollars per LYS. HPV screening resulted in similar costs and benefits, if the test cost is 5 US dollars and if 90% of women undergo follow-up after an abnormal screen. Cytology (Pap smear) was a reasonable alternative if sensitivity exceeds 80% and if 90% of women undergo follow-up. Compared with no screening, use of a combination of Pap smear and HPV testing at 5-year intervals in women of ages 20-70 could achieve greater than 90% reduction in cervical cancer mortality at a cost of 1683 US dollars per LYS, and VIA could achieve 83% reduction at 524 US dollars per LYS.Well-organized screening programs can reduce cervical cancer mortality in less-developed countries at low costs. These cost-effectiveness data can enhance decision-making about optimal policies for a given setting.

Abstract

The objective of the study was to assess the efficacy of cervical preparation with misoprostol or laminaria suction abortion up to 18 weeks gestation. The study was conducted among a consecutive case series of patients presenting for dilatation and evacuation at a single center. Cervical preparation was effected by either 600 mg buccal misoprostol (n = 32) or laminaria (n = 78). Dilatation and evacuation was then performed using vacuum aspiration, with fetal parts or placenta removed as necessary with appropriate forceps. The principle outcome of interest was procedure time. Complete abortion was effected in 100% of the cases. In all cases, the cervix was adequately prepared to allow either the introduction of a size 14-mm suction cannula or was easily dilated to this diameter. Group size was sufficient for detection of a 20% difference in mean procedure time with 80% power (calculated with two separate standard deviations for procedure time). Procedure times were not significantly different when misoprostol was used compared to laminaria for cervical preparation. It is concluded that the use of misoprostol to provide cervical preparation in second trimester abortion procedures appeared effective and offers an alternative to laminaria. Buccal misoprostol should be more widely investigated for this purpose.

Abstract

To estimate the inter-rater agreement on the assessment of cervical photographs after acetic acid wash, using visual inspection with acetic acid categories.Three raters individually assessed 144 photographs as negative, positive, or suspicious for cancer. The inter-rater agreement was analyzed using the unweighted and weighted kappa coefficient. To explore the reasons for concordancy and discordancy, photographs were compared on histologic evidence of cervical intraepithelial neoplasia and on testing for oncogenic types of human papillomavirus.Overall raw agreement among the three raters was 66.7% (96 of 144) with a kappa of 0.57 (95% confidence interval 0.48, 0.66). Pair-wise agreement using unweighted and weighted kappa was moderate to substantial: 0.54-0.60 and 0.56-0.63, respectively. There was concordance on negative in 25.7% (37 of 144) and on positive or suspicious for cancer in 41.0% (59 of 144). Cervical intraepithelial neoplasia II or III was not present on biopsy if photographs were concordant-negative, and the human papillomavirus test was less likely to be positive (relative risk 0.3; 95% confidence interval 0.2, 0.6) in concordant-negatives compared with concordant-positives, including suspicious for cancer. Cervical intraepithelial neoplasia II or III was more common in photographs that were concordant-positive, including suspicious for cancer, compared with discordants (relative risk 3.4, 95% confidence interval 1.5, 7.6).Based on photographs of the cervix taken after acetic acid wash, the level of agreement among raters using visual inspection with acetic acid categories was moderate to substantial, consistent with other commonly used tests.

Abstract

Typical failure rates for oral contraceptives remain much higher than ideal failure rates. Patients can cite the pill's perceived risks more readily than its benefits, and many women use oral contraceptives inconsistently or discontinue them entirely without a medical reason. Successful use of oral contraceptives mandates that we rethink our roles as providers. Medical barriers, such as mandatory pelvic examinations, impede clients' access to services and require reevaluation. Efforts must also focus on thorough, individualized counseling. Because compliance poses difficulties for many women and noncompliance results in reduced efficacy, counseling must address content points relevant to proper, consistent use. Additionally, as unexpected side effects often cause frustration and method discontinuation, counseling should anticipate their occurrence. Adolescents present additional challenges. However, with careful attention to concerns relevant to teenage women and consideration of obstacles to compliance, oral contraceptives can indeed be used successfully in this group. Regardless of age, all clients should receive information regarding emergency contraception, and instructions for pill use should be individualized to meet the needs of each patient.

Abstract

As part of a study to assess the role of cervical ectopia in the acquisition of cervical infections, we determined the reliability of cervical ectopia measurements made by computer planimetry and by clinical (visual) assessment.We conducted pelvic examinations of 1004 women seeking contraceptive services at two health centers in Baltimore. After application of acetic acid, clinicians estimated the relative area of ectopia by visual inspection and took cervical photographs. Two independent raters measured the absolute and relative areas of ectopia from the digitized images by means of an analytic software program. Agreement levels between raters, between multiple readings by the same rater, and between the two measurement methods were quantified by means of the intraclass correlation coefficient and weighted kappa.Intrarater agreement was excellent for computer planimetry measurements of the absolute (intraclass correlation coefficient, 0.97) and relative (intraclass correlation coefficient, 0.89) areas of ectopia. Interrater agreement was also high for computer planimetry measurements of the absolute (intraclass correlation coefficient, 0.83) and relative (intraclass correlation coefficient, 0.85) areas of ectopia. Agreement levels were moderate between clinician assessment and computer planimetry measurements of the relative area of ectopia (kappa = 0.48), but agreement was better when clinical assessment was limited to observations by a single, experienced clinician.Measurement of cervical ectopia by computer planimetry was highly reliable and appears appropriate for assessment of the role of ectopia in the acquisition of cervical infections. Clinical assessment of cervical ectopia may be used when computer planimetry is not available.

Abstract

Gynecologic endoscopic procedures are increasingly common and require the ability to control large vascular structures.The Filshie clip is a silicone-lined, titanium occlusive device, originally designed and Food and Drug Administration (FDA) approved for surgical contraception. This device also has the potential for occluding vascular structures during laparoscopic surgery.We describe a salpingectomy, an excision of bilateral hydrosalpinges, and a salpingo-oopherectomy. We performed all procedures laparoscopically using this device as the primary modality for assuring hemostasis.The Filshie clip is a useful and economical device for assuring hemostasis during gynecologic endoscopic surgery.

Abstract

Human pluripotent stem cells (hPSCs) have been derived from the inner cell mass cells of blastocysts (embryonic stem cells) and primordial germ cells of the developing gonadal ridge (embryonic germ cells). Like their mouse counterparts, hPSCs can be maintained in culture in an undifferentiated state and, upon differentiation, generate a wide variety of cell types. Embryoid body (EB) formation is a requisite step in the process of in vitro differentiation of these stem cells and has been used to derive neurons and glia, vascular endothelium, hematopoietic cells, cardiomyocytes, and glucose-responsive insulin-producing cells from mouse PSCs. EBs generated from human embryonic germ cell cultures have also been found to contain a wide variety of cell types, including neural cells, vascular endothelium, muscle cells, and endodermal derivatives. Here, we report the isolation and culture of cells from human EBs as well as a characterization of their gene expression during growth in several different culture environments. These heterogeneous cell cultures are capable of robust and long-term [>70 population doublings (PD)] proliferation in culture, have normal karyotypes, and can be cryopreserved, clonally isolated, and stably transfected. Cell cultures and clonal lines retain a broad pattern of gene expression including simultaneous expression of markers normally associated with cells of neural, vascular/hematopoietic, muscle, and endoderm lineages. The growth and expression characteristics of these EB-derived cells suggest that they are relatively uncommitted precursor or progenitor cells. EB-derived cells may be suited to studies of human cell differentiation and may play a role in future transplantation therapies.

Abstract

To test whether the performance of visual inspection using acetic acid (VIA) could be improved through adjunctive testing and to determine whether the combination of visual inspection of the cervix and HPV testing could prove useful for identifying those at highest risk of cervical precancer.Between October 1995 and August 1997, 2199 women willing to be screened for cervical cancer in peri-urban clinics in Harare, Zimbabwe received VIA, Pap smear and HPV as screening tests. The presence or absence of (pre)cancer was confirmed via colposcopy with biopsy as indicated for >97% of all women. Computerized simulations of sequential testing scenarios provided estimates of the joint (net) test qualities of different paired combinations of the three tests and allowed for comparisons with the individual test qualities.Using HGSIL/CIN II-III as the reference threshold of disease, the net sensitivity and specificity of VIA and HPV when used sequentially were 63.6 and 81.9%, respectively, compared to 43.3 and 91%, respectively, when Pap smears were followed by HPV testing. VIA followed by the Pap smear yielded a net sensitivity of 37.5% and net specificity of 94.3%.For programs with limited resources but with the capacity for HPV testing, sequential testing involving the use of VIA followed by HPV could yield fewer false positives than the use of VIA alone at a cost of relatively few additional false negatives.

Abstract

The current literature reflects three routes toward improving cervical cancer screening. The first is to improve the test qualities of cytology-based screening. The use of liquid-based cytology and computerized analysis of Papanicolaou tests are examples of attempts at this approach. Secondly, through various combinations of parallel or sequential tests, either the sensitivity or the specificity of a given test could be improved depending on the tests chosen and the order in which they were performed (eg, Papanicolaou test followed by human papillomavirus [HPV] or vice versa). Several excellent studies have been published this year on the use of HPV DNA testing as a primary screening modality and as an adjunct to the triage of mildly abnormal cytologic findings. The recent literature also reflects increasing interest in visual inspection of the cervix and self-collected samples for HPV testing as an equally effective and viable alternative to cytology in low-resource settings. A third possibility is to make use of advances in digital and spectroscopic techniques. In these cost-conscious times, a significant number of articles address the cost-effectiveness of these technologies and the real value of cervical cancer screening. This article reviews the current literature concerning both the advent of new cervical cancer screening technologies and the rediscovery of old ones.

Abstract

In developing countries, cervical cancer remains a clinical problem of public health proportions. Eighty percent of the approximately 400,000 new cases of cervical cancer each year occur in such settings. Primarily as a result of the introduction and success of screening programs, cervical cancer rates in developed countries have dropped remarkably. However, in most developing countries, screening programs are virtually nonexistent. Reasons for this relate primarily to lack of public awareness and the fact that screening via cytology is an untenable proposition for mass screening in such low-resource settings. Matching the resources available to provide cervical cancer screening in such settings requires alternative means of providing testing and treatment. Recent evidence indicates that, depending on local conditions and locally-made decisions, visual inspection of the cervix with acetic acid wash, coupled with a benign form of therapy, such as cryotherapy, could hold promise as a means of testing and treatment. By adapting resource-appropriate technologies and building local consensus regarding clinically driven public health approaches that are safe and feasible, the challenge of reducing the mortality from cervical cancer in developing countries can yet be met.

Abstract

We determined the utility of an assay for 13 cancer-associated HPV types in primary cervical cancer screening of Zimbabwe women at high risk of HIV infection. HIV antibody status was determined by ELISA of oral mucosal specimens, and HPV DNA in the genital tract was identified by hybridization of cervical scrapes with probe B of Hybrid Capture II. Among the 466 women investigated, the prevalence of HPV, low-grade squamous intraepithelial lesions (LGSIL) and high-grade SIL (HGSIL) were 47.2%, 13.9% and 12%. Fifty-three and one-half percent of the women were HIV-seropositive. As compared with HIV-seronegative women, HIV-infected women had a greater than 2-fold HPV prevalence (64.3% vs. 27.6%), a greater than 7-fold amount of HPV DNA (RLU of 82.6 vs. 10.7) in HPV(+) women assessed as normal on the reference standard, and a nearly 3-fold greater HGSIL prevalence (17.3% vs. 5.9%). The strong link between HGSIL and HPV DNA positivity was seen in both HIV-infected and HIV-seronegative women. The amount of HPV DNA increased with disease severity in both HIV-seronegative and HIV-infected women. The sensitivity and specificity of the HPV test for HGSIL were, respectively, 90.7% (95% confidence limit 77.9-97.4%) and 41.3% (34.5-48.3%) in HIV-infected women and 61.5% (31.6-86.1%) and 74.5% (68.0-80.3%), respectively, in HIV(-) women. The usefulness of the HPV test as a screening test for cervical cancer in areas of high HPV prevalence will depend upon local health resource availability, disease priorities and policies regarding clinical case management.

Abstract

To determine the utility of an assay for high risk genital human papillomavirus (HPV) in cervical screening in Zimbabwe, Africa.Cross-sectional study.Harare, Zimbabwe.Zimbabwe women (n = 2,140), 25 to 55 years old, recruited in clinics in Chitungwiza and Greater Harare.Genital specimens were assessed for HPV, using the HPV DNA test Hybrid Capture II (probe B). Further assessment of the women was conducted using colposcopy and biopsy as indicated. High grade squamous intraepithelial lesions were diagnosed in 215 women. Colposcopy and/or biopsy showed low grade lesions in 346 women.The overall prevalences were: 42 x 7% for HPV, 10% for high grade squamous intraepithelial lesions and 16% for low grade lesions. Prevalence for HPV decreased significantly with increase in age (P for trend < 0 x 0001) and increased significantly with increasing disease severity, from 35% in normal women, to 53% in women with low grade lesions and 81% in women with high grade lesions (P for trend < 0 x 001). In specimens positive for HPV, the amount was 14-fold higher in women with high grade lesions compared with normal women. In screening for high grade lesions the assay for HPV had a sensitivity of 81% (CI 75%-86%); sensitivity for low grade lesions was 64% (CI 60%-68%). Specificity was 62% (CI 59%-64%) for high grade lesions and 65% (CI 62%-67%) for low grade lesions. The positive predictive value was 19% (CI 17%-22%) for high grade lesions and 39% (CI 36%-42%) for low grade lesions.For high grade squamous intraepithelial lesions the sensitivity of the Hybrid Capture II HPV DNA test was high, but the specificity was relatively low. The test may therefore be most useful in conjunction with other screening tests.

Abstract

The objective of this study was to time the onset of contraceptive effectiveness in Norplant implant users, when the capsules were inserted beyond the first 7 days of the cycle, based on the immediate effect on the ovarian activity. A total of 42 healthy women requesting Norplant implant contraception were enrolled at clinics in Santo Domingo, Dominican Republic, and in Baltimore, Maryland. Implants were inserted on days 8-13 of the menstrual cycle. Blood samples for estradiol (E2), progesterone (P), luteinizing hormone (LH) (in a subset of 12 women), and levonogestrel (LNG) assay, were taken at 0 h and at 6, 12, 24, 72, and 168 h postinsertion. Ovulation, as defined by P > 2.5 ng/mL, occurred in 40% of subjects. A short lasting, frequently blunted, LH peak occurred within 12 h postinsertion, in all these subjects. The remaining subjects had anovulatory cycles with two distinct E2 profiles: continuously increasing E2 levels to a high mean of 414.3 pg/mL (28%), or no sustained increase in E2 (32%). Most cycles (86%) in which Norplant was inserted with high E2 levels (> 175 pg/mL) were ovulatory, whereas none were ovulatory with low E2 (< 100 pg/mL) at insertion. Based on the endocrine effects of Norplant implant insertion in the midadvanced follicular phase, in which ovulation will either occur within 48 h of insertion or will be impaired, additional contraceptive protection is necessary only for 3 days.

Abstract

This study was conducted to assess providers' attitudes toward the provision of long-term methods of contraception, in particular the IUD, and provider concerns about human immunodeficiency virus (HIV) in the context of family planning (FP) services. The data were collected using self-administered structured questionnaires. Between 65% and 80% of the public and private providers thought that the IUD is a good contraceptive method for Zimbabwean women. In addition, the majority of these two provider groups felt that neither the IUD nor tubal sterilization (TL) posed much risk of HIV infection to the client. A significant number of providers (especially the public nurses), however, thought that the provision of TL put the provider at high risk of HIV infection and a significant proportion of public nurses were also concerned about provider risk associated with providing IUD and injectables. To address such concerns, future training interventions should emphasize appropriate infection prevention practices associated with surgical FP method provision. Nurses, in particular, should be informed about the magnitude of risk associated with FP service provision and ways to protect themselves. Logistic activities also need to be strengthened so that legitimate concerns among providers regarding lack of adequate infection prevention supplies (e.g. gloves) in the field can be addressed.

Abstract

To provide scientific data regarding the changes in cervical mucus within the first hours to days after Norplant implant insertion and to estimate when the cervical mucus is hostile enough to suggest a contraceptive effect.Multicenter, clinical descriptive study.Family planning clinics.Forty-two women who were between days 8 and 13 of their menstrual cycle and who had requested Norplant implants were admitted to the study.Cervical mucus and blood samples were obtained.Cervical mucus scores, sperm penetration distances, and serum levels of progesterone, estradiol, and levonorgestrel.The median cervical mucus score observed at baseline was 6 ("fair"), indicating that the mucus was already somewhat hostile before insertion of the Norplant implants. The median scores declined to 5 at 12 and 24 hours and continued to decrease through day 7 to 2 ("poor"), a score that is judged as hostile to sperm penetration. Overall, 73% of all subjects had a poor cervical mucus score by 3 days after insertion; at 7 days after insertion, 90% exhibited poor mucus and none had a good score. There was a substantial drop in the overall median distance traveled by the vanguard sperm after 12 hours for each cervical mucus score grouping. The distance traveled decreased rapidly between 12 and 24 hours to < 0.5 cm in subjects with fair and poor mucus, and by day 3, 91% of the subjects exhibited poor sperm penetration.On the basis of our findings, deterioration of the quality of the cervical mucus and sperm penetration is evident by 24 hours after insertion, although not to a level that would suggest adequate protection until 72 hours after insertion. Therefore, we are confident in recommending that backup methods of contraception (e.g, condoms) need not be used for more than 3 days after insertion, even when the implants are inserted close to ovulation. These findings provide policy makers, clinic managers, and clinicians with important information about how they can improve client access to Norplant implants.

Abstract

Improperly placed Norplant implants pose a risk to neurovascular structures at the time of removal. Appropriate attention to insertion and removal should minimize the chance of injury. However, when injuries do occur, a logical and systematic approach to evaluation of the injury can help predict the outcome and establish a plan of care for the patient.

Abstract

To determine the learning curves and rapidity with which clinicians become competent in implant removal using two Norplant removal techniques.Twenty-four physicians, none of whom were experienced in the use of Norplant implants, were randomly assigned to learn either the "U" removal technique or the standard technique. The physicians in the two groups received identical training in all other respects. Each physician then performed ten supervised removals. Removal times, procedure problem rates, and the number of procedures performed by the clinicians before they were judged "competent" were assessed for both groups.Data from 240 removals were analyzed. Mean removal times were 38% faster in the "U" group than in the standard group. None of the "U" group procedures took longer than 20 minutes, compared with 11% of removals in the standard group (P < .001). The mean number of cases required before the provider consistently performed all steps adequately was significantly (P < .02) higher in the standard group (5.8 cases) than in the "U" group (3.9 cases).Using competency-based training methods, the "U" removal technique was learned easily by inexperienced clinicians. It appears to offer significant improvements in speed and achievement of proficiency over the standard technique recommended by the manufacturer. Large-scale programs should consider using competency-based training and the "U" technique as the removal method of choice when providing training in implant removal.

Abstract

The purpose of this study was to evaluate the safety, efficacy and acceptability of Lea's Shield, a new vaginal contraceptive barrier device, when used with either spermicidal or non-spermicidal lubricant. One-hundred-eighty-five (185) women enrolled at six centers. Half were randomized to use the device with spermicide and half with a non-spermicidal lubricant. To be eligible, volunteers had to be 18-40 years old (inclusive), in good health with regular menses, sexually active in an ongoing relationship and at risk for pregnancy, and willing to use Lea's Shield as their sole means of contraception for six months. Participants were seen at admission, one week, one month, three months and six months. Gross cumulative life table rates were calculated for pregnancy and others reasons for discontinuation. Adverse experiences and responses to an acceptability questionnaire were evaluated. One-hundred-eighty-two (182) volunteers contributed data to the analysis of safety and 146 to that of contraceptive efficacy. The unadjusted six-month life table pregnancy rate was 8.7 per 100 women for spermicide users and 12.9 for non-spermicide users (p = 0.287). After controlling for age, center, and frequent prior use of barrier methods, the adjusted six-month life table pregnancy rate was 5.6 for spermicide users and 9.3 for non-spermicide users (p = 0.086), indicating that use of spermicide lowered pregnancy rates, although not significantly, during typical use. For purposes of comparison, it is important to note that this study differed from the cap/diaphragm and sponge/ diaphragm studies in that a high percentage (84%) of volunteers were parous. For reasons that are unclear, pregnancy rates among parous women using barrier contraceptives tend to be higher than among nulliparous women. Indeed, in this study there were no pregnancies among nulliparous users of Lea's Shield. Standardization of parity of this study population on those of the cap/diaphragm and sponge/diaphragm studies suggests that unadjusted pregnancy rates for this device would have been considerably lower (2.2 and 2.9 per 100 users of spermicide and non-spermicide, respectively) had the study been done using the populations of earlier studies. Since no directly comparative study has been done, these figures provide a tentative estimate of the relative efficacy of Lea's Shield compared with the sponge, cap, and diaphragm. There were no serious adverse experiences attributed to the use of Lea's Shield. Acceptability was very good. Seventy-five percent (75%) of women responded to an end-of-study questionnaire; 87% of these reported that they would recommend Lea's Shield to a friend. Lea's Shield is a new vaginal contraceptive that does not require clinician fitting. Pregnancy rates in this study compare favorably with other studies of barrier contraceptive methods including the cervical cap, diaphragm, and sponge, even though this study was done with greater rigor and with a greater percentage of parous women than previous barrier studies. Lea's Shield appears to be safe and very acceptable to study volunteers.

Abstract

Removal of contraceptive implants (e.g. Norplant) is an issue affecting its worldwide acceptability. Reports of difficult, painful removals have resulted in lawsuits and reduced demand. To improve quality of care, we developed a scoring system to anticipate difficult removals. We report on the usefulness of such a system and present client perspectives about the removal experience.A 9-point scoring system based on the visibility, arrangement, and position (VAP) of Norplant capsules was used to assess the anticipated difficulty of removal in 53 consecutive patients. The VAP score was then correlated with removal time and related parameters.Mean removal time was 14.74 min (range 4.75-47). In 20% of patients, the VAP score indicated a potentially difficult removal and the VAP score correlated significantly with removal time (r = 0.3, p = 0.05). Patients expected removal to be moderately difficult (mean visual analog score 4.7 out of a possible 10), but after removal they rated the actual removal experience as relatively easy (mean score 2.6/10). Before the removal, only 48% of patients said they would recommend Norplant to a friend but after removal, 70% said they would do so.A scoring system such as the VAP score can help identify potentially difficult removals so that an experienced remover can be present at the time of removal or an appropriate referral made. However, the VAP score cannot predict variables such as the density of the subcutaneous fibrous tissue "envelope". Although patient anxiety concerning removal may be high, the presence of a competent remover and an easy removal experience reduces this anxiety and encourages patients to be more positive about this method. The value of having properly trained, competent personnel available to perform removals cannot be over-emphasized.

LAPAROSCOPIC STERILIZATION IN THE SUPINE POSITION USING THE RAMATHIBODI UTERINE MANIPULATORFERTILITY AND STERILITYBlumenthal, P. D.1995; 64 (1): 204-207

Abstract

To investigate the usefulness of the Ramathibodi uterine manipulator (AMZURA Enterprises, Freeport, NY) in performing laparoscopic sterilization procedures in the supine position under local anesthesia.Descriptive prospective study.Ambulatory surgical unit of university-affiliated hospital.Women presenting for elective sterilization and weighing < 110 kg.The Ramathibodi uterine manipulator was used to provide uterine manipulation in 85 cases of laparoscopic sterilization, all performed in the supine position as local anesthesia-sedation sterilization operations. Because such procedures are becoming more common worldwide, we propose the acronym "LASSO" (Local Anesthesia-Sedation Sterilization Operation) for this class of operations. Although commonly used in minilaparotomy procedures, use of this uterine manipulation device in laparoscopic procedures has not been published previously.Successful tubal occlusion.Among the 85 cases reported here there were no failures to manipulate the uterus successfully, to identify the tubes, and to occlude them.The simplicity of the Ramathibodi uterine manipulator provided several advantages over other means of uterine manipulation, notably [1] constant easy-to-learn maneuvers, [2] no tenaculum or balloon requirement, [3] the procedure could be performed in the supine position, and [4] there are no working parts, screws, or springs that could be lost or broken by operating room staff. Our experience with this device leads us to recommend it to colleagues as an inexpensive, safe, and effective alternative to currently available instruments for providing uterine elevation during laparoscopic sterilization procedures.

Abstract

Between January 1992 and January 1993, there were 280 teens (ages 13-18) who either delivered a baby or terminated a pregnancy at Johns Hopkins Bayview Medical Center. Of these, 92 chose to contracept with Norplant implants, and 188 chose another method including "no" method. In July 1993, telephone interviews were conducted with 37 of those who chose Norplant implants and 41 of the non-Norplant implants users. After 1 year, 47% of oral contraceptive (COC) users had discontinued the method compared to only 16% of Norplant implants users (P < 0.03). Reasons for discontinuation centered on side effects for both groups but with some COC and condom users, discontinuing use due to "forgetfulness" or failure (pregnancy). Among the COC group (which was the most common choice after Norplant implant), 25% of the adolescents had experienced a subsequent unplanned pregnancy compared to 0% of the Norplant implant group (P < 0.01). Norplant implants were clearly an acceptable and effective contraceptive for these post-partum and post-abortal teens, who articulated a high motivation to avoid a subsequent unplanned pregnancy. However, it is clearly not the only method teens will choose to use, and more attention must be paid to adequate counseling of those choosing another method.

Abstract

The analgesic efficacy of a single dose of ketorolac or ibuprofen given preoperatively was assessed in healthy outpatients undergoing general anesthesia for laparoscopic tubal ligation. Fifty patients were randomized to receive either ketorolac 60 mg intravenously (i.v.), ibuprofen 800 mg orally, or placebo in a double-blind manner. Anesthesia was induced with fentanyl 2 micrograms/kg, thiopental 5 mg/kg, and either vecuronium 0.1 mg/kg or succinylcholine 1.5 mg/kg i.v. and was maintained with nitrous oxide 67% in oxygen and isoflurane. Patients were assessed at 15-min intervals in the postanesthesia care unit (PACU) and treated for pain with i.v. morphine by protocol. Patients were evaluated for pain, analgesic requirements, side effects, and recovery times. After discharge, patients completed questionnaires to assess pain, analgesic use, and side effects 6 and 24 h postoperatively. Parenteral morphine was required in 80% of patients in the control group, and 73% of patients in both treatment groups, and the difference was not statistically significant. The dose of parenteral morphine required in the PACU was not different between the control (7 +/- 1.2 mg), ibuprofen (5.7 +/- 1.4 mg), and ketorolac (6.1 +/- 1.4 mg) groups. There was no difference between groups in terms of pain visual analog scale (VAS) scores, fatigue VAS scores, recovery times, or the incidence of postoperative nausea and vomiting. The preoperative administration of either parenteral ketorolac or oral ibuprofen did not decrease postoperative pain or side effects when compared to placebo in this outpatient population.

Abstract

Traditionally, management of incomplete abortion involves use of D&C or suction curettage in the operating room. Such management is costly and time-consuming. In order to potentially save time and money, we studied the use of manual vacuum aspiration curettage (MVAC) for the management of this problem.Data on hospital charges and times (e.g. waiting time, procedure time) were obtained for all cases of incomplete abortion presenting to hospital between January 1990 and July 1992. Between January 1990 and July 1991, all cases were managed traditionally. After July 1991, all cases were managed using MVAC in either the emergency room or the labor ward.Compared to the use of electrical suction equipment in the operating theatre, MVAC procedures resulted in significant savings in terms of both waiting times and costs. Waiting time was reduced by 52% and procedure time was reduced from a mean of 33 min to 19 min (P < 0.01). Total hospital costs were reduced by 41% (P < 0.01).Use of manual vacuum aspiration curettage in the management of incomplete abortion can reduce hospital costs and save time for both patients and clinicians.

Abstract

To compare acceptability, tolerance of side effects, and continuation rates among adolescent and adult Norplant accepters.An 18-month observational study was conducted of 136 adolescents and 542 adults who received Norplant at the Francis Scott Key Medical Center in Baltimore, Maryland. Data were collected from the following: a self-administered history form completed at the preinsertion visit, a self-administered follow-up form completed at routine follow-up visits, problem-visit chart review, and telephone contact for patients noncompliant with follow-up appointments.The adolescents ranged in age from 13-18 years (mean 16.4), and adults ranged in age from 19-46 (mean 24.7). The mean parity among teenagers was 1.4; among adults, 3.2. Thirty-nine percent of teenagers and 64% of adults had had one or more therapeutic abortions. Forty percent of adolescents and 47% of adults reported at least one contraceptive failure in the past. Both adolescent and adult Norplant accepters made few telephone calls or problem visits because of complaints or side effects. Compliance with routine annual follow-up was poor for adolescents (24 of 136, 18%) and adults (72 of 542, 13%). Follow-up of noncompliant patients revealed low rates of implant removal. Fifteen adolescents (11%) and 60 adults (11%) had Norplant removed. The most common reasons for removal included irregular bleeding, weight gain, headaches, and desire for pregnancy.Implant acceptability, continuation, and tolerance of side effects were high and comparable among adolescent and adult accepters. Initial implant users were primarily adolescents or adults who had experienced problems with other forms of reversible contraception. Adherence to scheduled follow-up appointments was poor, regardless of age.

Abstract

Norplant, the five-year subdermal contraceptive system, is the first implantable contraceptive method approved for general use in the United States. We describe the preliminary experiences of 246 U.S. women who accepted Norplant between April, 1991 and September, 1991. Norplant was well accepted among this diverse general population. Intensive counselling about side effects, especially menstrual changes, is crucial for patient satisfaction. Although 48% of acceptors experienced menstrual cycle changes and 70% experienced at least one side effect, phone calls and unscheduled visits for problems were infrequent. Adequate counselling about side effects obviates the need for a routine follow-up visit one month after insertion.

Abstract

In 1991, the abortion literature was characterized by articles relating to 1) epidemiologic issues in abortion care, 2) advances in knowledge and experience with medical abortifacients such as mifepristone (RU 486), and 3) cervical ripening prior to abortion with the use of both mifepristone and prostaglandins. Technical methods of achieving termination of pregnancy continue to be similar in the United States, the United Kingdom, and Europe, although induction-abortion times are generally slower in Europe than in the United States. Surgically, dilatation and evacuation procedures continue to be more common in the United States than in other countries. The effectiveness of mifepristone is undisputed, and the recommended dose for early first-trimester termination is being compared with lower dose alternative regimens. There is additional evidence that at least in the short term, the negative psychological sequelae of abortion are infrequent and are inconsequential as a public health issue.

Abstract

In 1990 abortion literature was characterized by articles relating to 1) the safety of surgical abortion procedures, 2) advances in knowledge and experience with medical abortifacients such as mifepristone (RU 486), and 3) reviews of psychologic and ethical considerations. Although technical methods differ greatly between countries and continents, there is increasing similarity between termination protocols in the United States, the United Kingdom, and Europe. The advent of mifepristone will make this even more so. Surgically, although dilatation and evacuation procedures are far more common in the United States than in other countries, the literature reflects a fine-tuning of analysis and technique, with safety the major consideration. Knowledge about the effectiveness of mifepristone continues to grow, and the effective dose for early first-trimester termination appears established. There is increasing evidence that at least in the short term, the negative psychologic sequelae of abortion are infrequent and are inconsequential as a public health issue.

Abstract

A day in obstetric-gynecologic practice in Kenya involves uterine rupture and other conditions resulting from inadequate care and facilities for labor, as well as infected abortions. Technology and equipment taken for granted in America either don't exist or don't work. Although practice is primitive in many ways, some of the concerns of doctors are the same as in developed countries.

Abstract

A randomized trial was conducted to evaluate the comparative effectiveness of Dilapan cervical dilators and Laminaria japonicum as cervical ripening agents before induction of labor at term. Patients with Bishop scores of 4 or less and a fetal or maternal indication for induction at 34 or more weeks' gestation were eligible for the study. The outcome variables of interest were Bishop score upon removal of the devices, number of devices used, induction-to-delivery time, and induction-to-complete dilatation time. In the Dilapan group, an average of 4.3 devices per patient was used, compared with 9.7 devices in the laminaria group (P less than .01). Among patients who eventually achieved complete dilatation, the mean (+/- SD) time for the Dilapan group was 10.8 +/- 6.1 hours, compared with 14.7 +/- 9.2 hours with laminaria. For women undergoing induction of labor at term with an unripe cervix, Dilapan appeared to be a preferable alternative to Laminaria japonicum because its use may result in a shorter induction-to-delivery interval with fewer devices required to obtain significant cervical ripening.

Abstract

In a prospective, randomized trial, 103 women underwent a total of 203 antenatal stress tests. One hundred four nipple stimulation contraction stress tests (BSTs) and 99 oxytocin challenge tests (OCTs) were performed. The patient populations were similar for the two groups. Uterine hyperstimulation with abnormal fetal heart rate patterns occurred with 2.9% and 1% of the BSTs and OCTs, respectively. The failure rate for the BST group was 22%. Maternal age and weight, parity and gestational age were not associated with test failure. Only one patient failed more than one BST, but she did not fail every such test. When test time (time from initiation to completion of the test) was compared between the two groups, a significant difference was found when the BST was successful. However, when test time in the total BST group (successful and unsuccessful BSTs followed by an OCT was compared to that in the OCT group, no difference could be found. Though an OCT following an unsuccessful BST took longer to perform than did a primary OCT, the difference was not statistically significant. It appears that BST test failure may relate more to the technique of nipple stimulation used than to intrinsic patient factors.

PROSPECTIVE COMPARISON OF DILAPAN AND LAMINARIA FOR PRETREATMENT OF THE CERVIX IN 2ND-TRIMESTER INDUCTION ABORTIONOBSTETRICS AND GYNECOLOGYBlumenthal, P. D.1988; 72 (2): 243-246

Abstract

Fifty-four women presenting for second-trimester induction abortion received either Dilapan synthetic dilators or laminaria for pretreatment of the cervix before induction abortion using intra-amniotic prostaglandin (PG) F2 alpha. The two groups were similar with respect to age, parity, previous abortion, and gestational age. Neither group experienced any unusual complications. The same protocol for intraamniotic PGF2 alpha (40 mg) was used in all patients except for three with histories of asthma, in whom PGE2 vaginal suppositories (20 mg) were used as the induction agent. For the Dilapan group, an average of three devices was used, compared with an average of six in the laminaria group. The mean (+/- SEM) induction-abortion time for Dilapan patients was 10.9 +/- 1.3 hours, compared with 16.1 +/- 1.4 hours in the laminaria group, a statistically significant difference (P less than .05). When nulliparous women were examined separately, the mean times were 11.0 +/- 1.7 for Dilapan and 16.5 +/- 1.6 for laminaria, a medically relevant and statistically significant difference (P less than .05). Dilapan appears to be an effective alternative to laminaria that results in shorter induction-abortion intervals.

Abstract

In order to obtain information necessary for optimum delivery of services, data were collected on the nature of the services provided at a family planing clinic. Clinic visits were divided into initial, annual, routine, problem, supply, educational and unknown. An analysis of the "problem" visits was undertaken to assess various epidemiologic aspects of such visits and to identify areas of clinic efficiency that could be improved. Problem visits were defined as any visits for which the patient had a presenting complaint. Age, level of education, method of contraception and parity were statistically associated with problem visits. When compared to Pill users, diaphragm users, intrauterine device users and non-users had a higher-than-expected number of problem visits. Less educated women and teenagers had a lower-than-expected number of problem visits when compared to more educated and older women. Socioeconomic status and problem visits were not statistically associated. Problem visits required more time, utilized more medical services and resulted in more referrals to the gynecology clinic than did other visit types. As a result of this analysis, we have increased our educational efforts for patients at high risk of problem visits and have instituted a special problem-oriented family planning clinic in which a full complement of house staff and ancillary personnel are available. This arrangement makes the uncomplicated family planning clinic run more smoothly and efficiently and obviates the need for time-consuming and cost-ineffective referrals.

Abstract

This report compares the effects of human menopausal gonadotropin (hMG) and purified urinary human follicle-stimulating hormone (hFSH) protocols in patients with irreparable tubal disease as the sole indication for in vitro fertilization-embryo transfer (IVF-ET). The hFSH protocol was associated with significantly more uniform folliculogenesis and more effective steroidogenesis than the one using hMG. In addition, the hFSH protocol showed a trend toward more oocytes per laparoscopy and more embryos per transfer than the hMG group, although the difference was not statistically significant. More oocytes in the hMG group were classified as immature when compared with the hFSH group (P less than 0.05). Pregnancy rates in both groups were not significantly different. An allergic drug reaction that occurred in one patient on the hFSH protocol is the first such reaction reported with hFSH in the literature. The hFSH protocol is associated with a trend toward parameters that correlate with improved success rates in the IVF-ET program.